How Do You Get a Fever? Symptoms and Common Causes

Fever starts in your brain, not at the site of infection. When your immune system detects an invader, it releases signaling molecules that ultimately reach a small region of the brain called the hypothalamus, which acts as your body’s thermostat. The hypothalamus then raises its target temperature, and the rest of your body scrambles to comply: you shiver, your blood vessels constrict, and your core temperature climbs. The whole process is surprisingly deliberate, more like someone turning up a dial than a system breaking down.

The Chain of Events That Produces a Fever

Most fevers begin with something foreign entering the body, whether that is a bacterium, virus, fungus, or parasite. These organisms carry molecules on their surfaces that your immune cells recognize as threats. Immune cells called macrophages respond by releasing a group of signaling proteins known as cytokines. These cytokines are the messengers that carry the alarm from the site of infection to the brain.¹

The problem is that the brain sits behind a tightly guarded barrier, the blood-brain barrier, that keeps most blood-borne substances out. Cytokines can reach the brain by crossing this barrier directly or by binding to receptors on cells lining the brain’s blood vessels.² When that happens, the blood vessel cells produce a molecule called prostaglandin E2. This is the critical chemical that actually changes the thermostat. Research has established that prostaglandin E2, by binding to receptors on brain endothelial cells, is the key trigger that resets the hypothalamic set-point upward.³

Inside the hypothalamus, prostaglandin E2 changes how temperature-sensing neurons fire. Normally, “warm-sensitive” neurons increase their activity when they detect warmth, which triggers cooling responses like sweating and opening blood vessels near the skin. Prostaglandin E2 suppresses those warm-sensitive neurons while activating temperature-insensitive neurons, effectively telling the brain that the body is too cold even when it is not.⁴ The result is that your hypothalamus now “wants” a temperature of, say, 39°C instead of the usual 37°C, and it activates every tool at its disposal to get there.

Why You Shiver and Feel Cold

Once the set-point shifts upward, your brain perceives your current normal temperature as too low. This mismatch is why people with a rising fever often feel intensely cold and reach for blankets, even though their skin may already be warm to the touch. Doctors sometimes call this the “chill phase.” Your body generates heat through several mechanisms simultaneously: brown fat tissue burns energy to produce warmth, skeletal muscles shiver, the heart rate increases, and blood vessels in the skin constrict to prevent heat from escaping.⁵

When the fever eventually breaks, either because the infection is being controlled or because you took an antipyretic, the set-point drops back down. Now the brain perceives the elevated body temperature as too high. The process reverses: blood vessels in the skin dilate and sweating kicks in, which is why people often feel flushed and damp as a fever resolves.⁶ That wave of sweating is not a sign of getting sicker; it is the body dumping excess heat now that the thermostat has returned to normal.

Symptoms That Accompany Fever

The temperature rise itself is only one part of what people experience. Many of the symptoms associated with fever are actually caused by the same cytokines that triggered the thermostat change, not by the heat itself. These include:

• Fatigue and malaise: cytokines promote “sickness behavior,” a coordinated response that conserves energy for fighting the infection.
• Muscle aches: inflammatory signaling sensitizes pain receptors throughout the body.
• Headache: changes in blood flow and inflammation in the meninges, the membranes surrounding the brain, contribute to the throbbing feeling common during fever.
• Loss of appetite: another cytokine-driven effect that shifts metabolic resources away from digestion.
• Increased heart rate: the cardiovascular system ramps up to support heat production and deliver immune cells more quickly.

If body temperature climbs very high or stays elevated for a prolonged period, the consequences become more serious. Cells and organs can be damaged when heat generation outstrips the body’s ability to lose heat, potentially leading to organ dysfunction.⁷ This is rare in typical fevers but becomes a real concern in extreme cases or in people who cannot regulate temperature well.

Common Infectious Causes

Infections are by far the most frequent reason for fever. Virtually any pathogen can trigger the cascade described above, but some of the usual suspects include:

• Respiratory viruses: influenza, COVID-19, RSV, and the common cold (less often) are among the most common sources of fever in adults and children alike.
• Bacterial infections: urinary tract infections, pneumonia, strep throat, and skin infections routinely cause fever. Bacteria release molecules like lipopolysaccharide (endotoxin) that are potent triggers of the cytokine cascade.
• Gastrointestinal infections: food poisoning from Salmonella, Campylobacter, or viral gastroenteritis often produces fever alongside nausea and diarrhea.
• Ear infections: particularly common in young children, otitis media frequently causes moderate fevers.

The classic pathway applies to all of these: pathogen enters the body, macrophages detect it, cytokines are released, prostaglandin E2 reaches the hypothalamus, and the set-point shifts upward.¹ The specific pathogen determines other symptoms, but the fever itself follows the same basic blueprint.

Non-Infectious Causes of Fever

Plenty of people develop fevers with no infection present. Autoimmune diseases like lupus, rheumatoid arthritis, and inflammatory bowel disease can drive the same cytokine cascade because the immune system is chronically activated against the body’s own tissues. Certain cancers, particularly lymphomas and leukemias, are associated with persistent or recurring fevers. Tissue damage from surgery, burns, or heart attacks can also release inflammatory signals that trigger a fever response.

Drug-induced fever is another common and frequently overlooked cause. Some antibiotics, anticonvulsants, and newer cancer therapies called immune checkpoint inhibitors can provoke fever as an adverse reaction. Checkpoint inhibitors are especially interesting because they work by unleashing the immune system against cancer cells, and the resulting immune activation can elevate cytokines enough to cause fever through the same pathways as infection.⁸ When a patient on these medications develops a persistent fever and no infection can be found, the drug itself is often the culprit.

Stress-Induced Fever

This one surprises most people: psychological stress can raise body temperature through mechanisms entirely separate from the inflammatory pathway that drives infectious fever. In what is sometimes called psychogenic fever, the sympathetic nervous system (the fight-or-flight system) activates heat production, particularly through brown fat tissue, without any involvement of the cytokines or prostaglandins that characterize pathogenic fever.⁹

Acute stress tends to produce a brief spike in core temperature that resolves once the stressor passes. Chronic or repeated stress can produce a subtler but more persistent pattern: slightly elevated temperature throughout the day and flattened day-night temperature cycles. In clinical case reports, even something as specific as a stressful interview has been shown to increase core temperature in patients with psychogenic fever, and blood tests confirmed that the typical fever-causing cytokines were not involved.¹⁰ Because the mechanism is different, standard fever-reducing drugs like ibuprofen and acetaminophen, which work by blocking prostaglandin production, are generally ineffective against psychogenic fever. Anxiolytics and stress management tend to be more useful.

Fever Versus Hyperthermia

People often use “fever” and “overheating” interchangeably, but they are fundamentally different processes. In fever, the thermostat is deliberately set higher, and the body’s regulatory machinery is working correctly to reach that new target. In hyperthermia, like heatstroke or malignant hyperthermia from anesthesia, the thermostat has not changed at all. Instead, the body is gaining heat faster than it can lose it, or its cooling mechanisms have failed.

This distinction matters for treatment. Aspirin-like drugs work well for fever because they block the prostaglandin E2 that shifted the set-point. They are useless for heatstroke, because no set-point has changed. Conversely, physical cooling (ice packs, cool water) is the primary treatment for hyperthermia but is largely ineffective during genuine fever, where the body will simply shiver harder to re-achieve the elevated set-point.¹¹ If you douse someone in a fever with cold water, their body fights back to stay warm. If you give aspirin to someone with heatstroke, you have wasted precious time.

Fever From Brain Injury

Damage to the hypothalamus itself can cause what is called central fever or neurogenic fever. This occurs in conditions like traumatic brain injury, stroke, or brain surgery that directly injure the temperature-regulating center.¹² Because the thermostat is physically damaged rather than being reset by prostaglandins, central fever does not respond reliably to standard antipyretics. It is a diagnosis of exclusion: clinicians need to rule out infection and drug reactions before concluding that the fever is neurogenic. Treatments that target the sympathetic nervous system, such as the beta-blocker propranolol, have shown some effectiveness in these cases.

Why Fever Exists at All

Given how miserable fever makes you feel, it is reasonable to wonder whether it serves any purpose. The evidence is strong that it does. Fever is not a glitch in the system. It is an ancient, conserved defense mechanism found across vertebrates, from fish and lizards to mammals.¹³ Cold-blooded animals cannot generate internal heat the way we do, so when infected, they deliberately seek warmer environments to raise their body temperature, a behavior called “behavioral fever.” Recent research found that this behavioral fever optimizes T cell immunity in fish, suggesting that the link between elevated temperature and immune function evolved before the first land-dwelling vertebrates even appeared.¹⁴

In mammals, moderate fever enhances multiple branches of the immune system. Elevated temperature speeds up the migration of neutrophils (first-responder immune cells), boosts the activation and proliferation of lymphocytes (the cells that target specific pathogens), and increases the production of cytokines that coordinate the immune response. There is also evidence that fever slows bacterial growth and viral replication, partly by reducing iron availability in the blood, which many pathogens need to thrive.¹⁵ Animal studies have generally found that moderate fevers decrease illness severity and improve survival rates during bacterial and viral infections.¹⁶ The fever response also confers a survival benefit during infection by enhancing both innate and adaptive immune responses through thermal stimulation.¹⁷

This is part of why the blanket advice to “take something for a fever” at the first sign of temperature elevation has drawn pushback from some researchers. A moderate fever in an otherwise healthy person may actually be helping. That said, very high fevers, fevers that persist, or fevers in vulnerable populations like the very young or very old deserve medical attention regardless of any theoretical benefit.

How “Normal” Temperature Varies

The familiar 37°C (98.6°F) figure dates back to a 19th-century German study and is treated as gospel by many people, but more recent systematic reviews paint a more nuanced picture. Average body temperature varies significantly depending on where you measure it. Rectal temperature averages about 37.04°C, oral about 36.57°C, and underarm (axillary) about 35.97°C.¹⁸ Temperature also fluctuates throughout the day, running lowest in the early morning and peaking in the late afternoon. Women tend to run slightly warmer than men, and normal temperature drifts lower with age.

All of this means that a rigid cutoff like “fever is anything above 38°C” is a simplification. If your baseline oral temperature runs around 36.3°C in the morning, a reading of 37.5°C could represent a meaningful increase for you even though it falls below the textbook fever threshold. This is especially relevant for older adults, whose baseline temperatures are often lower and whose fever response can be blunted.

Why Older Adults Sometimes Do Not Develop Fever

In people over 65, the immune and thermoregulatory systems are less responsive. Fever may be absent in roughly 20 to 30 percent of elderly patients with a serious infection.¹⁹ This is not because older adults do not get infections; it is because their bodies may fail to mount the full cytokine and prostaglandin cascade that produces the temperature spike. The result is that serious infections like pneumonia or urinary tract infections can present with vague symptoms, confusion, weakness, or falls, without an obvious fever to alert caregivers. For this reason, clinicians often use a lower temperature threshold (sometimes as low as 37.8°C orally, or even just a 1.1°C rise from baseline) when evaluating older adults for possible infection.

Febrile Seizures in Children

Febrile seizures are the most common type of seizure in infants and young children, typically occurring between 3 months and 5 years of age.²⁰ They are frightening to witness but usually harmless. The mechanism is not fully understood, but it involves the same cytokines that drive the fever. When cytokines cross the blood-brain barrier, they increase excitatory signaling between neurons while simultaneously dampening inhibitory signaling, which tips the developing brain toward a seizure threshold.²¹

Most febrile seizures are “simple,” meaning they last less than 15 minutes and do not recur within 24 hours. They do not cause brain damage and do not mean a child has epilepsy. Prolonged or repeated febrile seizures are less common but have received more research attention because of a possible link to later development of temporal lobe epilepsy. The relationship is actively studied, but it remains unclear whether the seizures themselves contribute to epilepsy risk or whether both share a common underlying vulnerability.²²

One widespread misconception is that aggressively treating a child’s fever with medications will prevent febrile seizures. Studies have not supported this idea. Seizures seem to be triggered by the rapid change in temperature and the cytokine storm more than by the absolute temperature reached, so giving acetaminophen or ibuprofen may make the child more comfortable but does not reliably prevent seizures.

How Fever-Reducing Drugs Work

Acetaminophen (paracetamol) and non-steroidal anti-inflammatory drugs like ibuprofen and aspirin all reduce fever through the same basic strategy: they inhibit cyclooxygenase (COX) enzymes, which are responsible for producing the prostaglandin E2 that resets the hypothalamic thermostat. By cutting off prostaglandin production, these drugs allow the set-point to drift back to normal, and the body’s cooling mechanisms do the rest.

Acetaminophen taken at a standard dose is a potent COX-2 inhibitor and may also inhibit COX-1.²³ Ibuprofen inhibits both COX-1 and COX-2 and has the added benefit of reducing inflammation at the infection site. Aspirin works similarly but is avoided in children due to the risk of Reye syndrome. All of these drugs address the prostaglandin pathway specifically, which is why they are effective against infectious fever but do little for hyperthermia, central fever from brain injury, or psychogenic fever, each of which involves a different mechanism.

It is worth noting that COX enzymes also play a role in normal, non-fever thermoregulation. There is evidence that acetaminophen can slightly lower core temperature even in people without fever, particularly in cool environments, because it may block the COX-mediated heat production that helps maintain normal body temperature under those conditions.²³ The effect is small but real, and it is a reminder that these pathways do more than just produce fevers.

Fever as a Medical Concept Through History

For most of recorded medical history, fever was not thought of as a symptom. It was the disease. The ancient Greek physician Galen treated fever as a systemic illness in its own right, and this understanding persisted for well over a thousand years. It was not until the 17th and 18th centuries that clinicians like Hermann Boerhaave began to see fever as one feature of a larger clinical picture rather than the problem itself. Around the same time, the work of Ignaz Semmelweis on puerperal (childbed) fever helped cement the idea that fever was a sign pointing to an underlying cause, in that case, bacterial contamination during childbirth.²⁴

Even with 20th- and 21st-century advances in immunology and neuroscience, fever remains a moving target. The cascade from pathogen to cytokine to prostaglandin to set-point shift is well-mapped in broad outline, but many of the intermediate steps involve competing candidate molecules whose relative importance is still debated.²⁵ The fact that fever can also arise from autoimmunity, cancer, drugs, stress, and brain injury, each through partially distinct mechanisms, makes it one of the most universal and yet least straightforward signs in medicine. Knowing which type of fever you are dealing with determines everything about how to treat it, which is exactly why the first question any clinician asks when evaluating a fever is not “how do we bring it down” but “why is it there.”