Sepsis is caused by the body’s own immune system overreacting to an infection. Any type of infection, whether bacterial, viral, or fungal, can trigger it. The infection itself doesn’t destroy your organs. Instead, your immune response spirals out of control and attacks your own tissues. Globally, sepsis affects an estimated 166 million people each year and is linked to roughly 21.4 million deaths.
How an Infection Becomes Sepsis
Most infections stay contained. Your immune system sends white blood cells to the site, fights off the invader, and the inflammation resolves. In sepsis, that process goes haywire. The immune system floods the bloodstream with signaling molecules called cytokines, which recruit more immune cells, which release even more cytokines. This feedback loop, sometimes called a “cytokine storm,” means the immune response stops targeting the original infection and starts damaging healthy tissue throughout the body.
Research from Harvard Medical School has shown that a specific signaling molecule promotes the production of inflammatory immune cells that are key sources of this cytokine storm. The result is widespread inflammation that can impair the lungs, kidneys, liver, and other organs simultaneously. It’s not the bacteria or virus doing the damage at this point. It’s your own defense system.
Bacteria Are the Most Common Trigger
About 90% of identified infectious agents in severe sepsis cases are bacteria. These fall into two broad categories based on their cell wall structure, and both are equally capable of triggering sepsis.
Gram-negative bacteria account for roughly 45% of identified cases. The most common of these is E. coli, responsible for about 13% of all identified sepsis cases. These bacteria carry a molecule on their outer surface that is particularly potent at activating the immune system.
Gram-positive bacteria account for about 35 to 43% of cases, with Staphylococcus species (including staph aureus) being the most frequent, found in around 30% of identified sepsis cases. Streptococcus species are another common gram-positive cause. The immune system detects these bacteria through different receptors than it uses for gram-negative bacteria, but the end result is the same inflammatory cascade.
Viral and Fungal Infections Can Also Cause It
Bacteria get the most attention, but viral and fungal infections trigger sepsis too. Influenza, COVID-19, and other serious viral infections can all set off the same dangerous immune overreaction. Fungal sepsis, often caused by Candida species, tends to occur in people with weakened immune systems, such as those on chemotherapy or long-term antibiotics that disrupt the body’s normal microbial balance. Fungal sepsis is less common but carries a high mortality rate because it’s often diagnosed late.
Where the Initial Infection Starts
Sepsis doesn’t appear on its own. It always begins with an infection somewhere in the body. The most common starting points are the lungs (pneumonia), the urinary tract, the abdomen (such as a ruptured appendix or infected gallbladder), and the skin or soft tissues (including surgical wounds and pressure sores). Bloodstream infections from IV lines or other medical devices are another frequent source, particularly in hospitalized patients.
Pregnancy and childbirth create additional entry points for infection. Premature rupture of membranes, cesarean delivery, and retained tissue after birth can all introduce bacteria. Maternal sepsis is the third most common cause of maternal mortality worldwide.
Who Is Most Vulnerable
Certain groups face a significantly higher risk of developing sepsis from what might otherwise be a manageable infection:
- Age: Adults 65 and older and children younger than one are at the highest risk.
- Chronic conditions: Diabetes, lung disease, and end-stage kidney disease (particularly in people on dialysis) increase susceptibility.
- Cancer: About 1 in 5 sepsis hospitalizations are cancer-related. Chemotherapy suppresses the immune system, making infections more likely and harder to fight.
- Weakened immune systems: This includes people on immunosuppressive medications, those with HIV, and organ transplant recipients.
- Recent hospitalization or surgery: Invasive procedures, IV lines, and catheters create opportunities for bacteria to enter the body.
- Previous sepsis: Survivors of sepsis are at higher risk of getting it again.
- Pregnancy and postpartum: Immune system changes during pregnancy, combined with medical procedures, raise infection risk.
How Sepsis Progresses to Septic Shock
Sepsis exists on a spectrum. In its earlier stages, the body compensates for the widespread inflammation. The heart pumps harder, breathing rate increases, and blood vessels dilate to try to maintain oxygen delivery. During this phase, the skin may still feel warm because blood flow to the surface is maintained.
When sepsis worsens into septic shock, the circulatory system begins to fail. Blood pressure drops so severely that it can’t be corrected with IV fluids alone. At the cellular level, tiny blood clots form in capillaries, blocking oxygen delivery to tissues. Blood flow gets diverted away from the smallest vessels where oxygen exchange actually happens. Cells begin producing energy without adequate oxygen, generating lactic acid as a byproduct. Rising lactate levels in the blood are one of the key markers that sepsis has crossed into shock.
In this later stage, the skin often becomes cool and mottled. The lungs, kidneys, and liver can begin failing in rapid succession. Septic shock carries a substantially higher mortality rate than sepsis alone, which is why early recognition matters so much.
Recognizing the Shift From Infection to Sepsis
The challenge with sepsis is that it often starts looking like any other infection: fever, feeling unwell, localized pain. The signals that something more dangerous is developing include a rapid heart rate, fast breathing (more than 22 breaths per minute), confusion or altered mental state, and a drop in blood pressure. Clinicians use a quick screening tool that checks these three specific signs: mental status changes, low blood pressure (below 100 systolic), and elevated breathing rate.
For anyone fighting an infection, the key warning signs are confusion that wasn’t there before, feeling dramatically worse rather than gradually better, breathing that feels labored or unusually fast, and skin that appears mottled or feels clammy. Sepsis moves fast. An infection that seemed routine in the morning can become life-threatening by evening, particularly in people with the risk factors described above.