A low white blood cell count (leukopenia) paired with low neutrophils (neutropenia) usually means your bone marrow isn’t producing enough immune cells, your body is destroying them too quickly, or something is interfering with their normal lifecycle. Neutrophils are the most abundant type of white blood cell and your first line of defense against bacterial infections, so when both numbers drop together, the underlying cause almost always traces back to neutrophil production or survival specifically.
Neutropenia is classified by severity based on your absolute neutrophil count (ANC): mild is 1,000 to 1,500 cells per microliter, moderate is 500 to 1,000, and severe is below 500. The lower your count, the higher your risk of infection. Understanding what’s driving your numbers down is the first step toward knowing what comes next.
Medications Are the Most Common Trigger
Drug-induced neutropenia is one of the most frequent explanations, particularly if your counts dropped after starting a new medication. The drug classes most often responsible include antibiotics, anti-seizure medications, antipsychotics, anti-thyroid drugs, blood thinners, and nonsteroidal anti-inflammatory drugs (NSAIDs). In most cases, the drop is reversible once the medication is stopped or adjusted.
Some drugs carry an especially high risk. Clozapine (used for treatment-resistant schizophrenia), anti-thyroid medications like methimazole, sulfasalazine (used for inflammatory bowel disease and rheumatoid arthritis), and the antibiotic combination trimethoprim-sulfamethoxazole are all well-documented offenders. In rare cases, genetic factors make certain people more vulnerable. For example, people who carry specific immune-system gene variants appear more susceptible to methimazole-induced neutropenia. Combining certain medications can also amplify the risk in ways neither drug would cause alone.
If you’ve recently started chemotherapy, low counts are expected rather than surprising. Chemotherapy targets rapidly dividing cells, and the cells in your bone marrow that produce neutrophils divide quickly. This is the most predictable form of drug-induced neutropenia and is actively managed by oncology teams, sometimes with growth factor injections that stimulate the bone marrow to ramp up neutrophil production.
Viral and Bacterial Infections
Infections themselves can temporarily suppress white blood cell production, which sometimes creates a confusing picture: the very thing your immune system needs to fight is also weakening it. Several viruses are known to directly interfere with bone marrow function. HIV is a well-known cause, but cytomegalovirus (CMV), Epstein-Barr virus (the virus behind mono), influenza, hepatitis, and parvovirus B19 can all drive counts down.
CMV is particularly relevant because it hides inside the stem cells and early-stage immune cells in your bone marrow. It stays dormant there and can reactivate when your immune system is suppressed for other reasons, creating a cycle of worsening counts. Tuberculosis has also been linked to bone marrow disruption through its interaction with immune cells in the lungs and beyond. Most infection-related neutropenia resolves as the infection clears, though recovery can take weeks.
Autoimmune Diseases
In autoimmune neutropenia, your immune system mistakenly produces antibodies that target and destroy your own neutrophils. This can happen on its own (primary autoimmune neutropenia, which is relatively common in infants and young children) or as part of a broader autoimmune condition.
Lupus is one of the strongest autoimmune associations. Research has shown that people with lupus who have chronically low neutrophil counts often test positive for anti-Ro/SSA antibodies. These antibodies appear to cross-react with proteins on the surface of neutrophils, triggering the immune system’s complement cascade, essentially marking the neutrophils for destruction. Rheumatoid arthritis, Sjögren’s syndrome, and other systemic autoimmune conditions can cause similar patterns through related antibody-driven mechanisms. The common thread is a breakdown in the immune system’s ability to distinguish its own cells from threats.
Bone Marrow Disorders
Since white blood cells are manufactured in the bone marrow, diseases that damage or crowd out healthy marrow tissue directly reduce production. Aplastic anemia is one of the most serious examples. In this condition, the bone marrow fails to produce enough of all blood cell types, not just white cells. Counts for red blood cells and platelets typically drop alongside neutrophils.
Myelodysplastic syndromes (MDS) represent another category where the bone marrow produces blood cells that are abnormal and don’t function properly. Some of these defective cells die before they ever leave the marrow. Leukemia and other blood cancers can physically replace healthy marrow with malignant cells, crowding out the space where neutrophils would normally be made. When cancer from other parts of the body spreads to the bone marrow, it can cause the same problem.
Nutritional Deficiencies
Your bone marrow needs specific raw materials to build neutrophils, and running short on certain nutrients can slow or halt production. Vitamin B12, folate, and copper are the three nutrients most directly linked to neutropenia. B12 and folate are essential for DNA synthesis in rapidly dividing cells, which includes the precursor cells in your marrow. Copper plays a role in the maturation process that turns immature marrow cells into functional neutrophils.
Nutritional neutropenia tends to develop gradually and is more common in people with absorption issues (such as celiac disease or after gastric bypass surgery), strict dietary restrictions, or chronic alcohol use. The good news is that counts typically recover once the deficiency is corrected, though it can take several weeks for the bone marrow to catch up.
Benign Ethnic Neutropenia
Not every low neutrophil count signals a problem. Benign ethnic neutropenia (BEN) is a genetic variation that commonly affects people of African and Middle Eastern descent. It’s not a disease and doesn’t increase infection risk. In one study of breast cancer patients of Middle Eastern ethnicity, 14.6% had a presumed diagnosis of BEN.
People with BEN carry what’s known as the Duffy-null phenotype on their red blood cells, which serves as a genetic marker for the condition. Their neutrophil counts naturally run below the standard reference range, but their immune function is normal. This distinction matters because people with BEN sometimes face unnecessary treatment delays, particularly during chemotherapy, when doctors hold doses based on lab numbers that are actually normal for that individual. Evidence shows these patients are not at increased risk of infection, and recognizing BEN can prevent gaps in care that don’t need to happen.
How the Cause Is Identified
The starting point is a complete blood count (CBC) with a differential, which breaks down your white blood cells by type and shows exactly which populations are low. If neutrophils are selectively reduced while other white blood cell types remain normal, that narrows the possibilities. If all cell lines are low, that points more toward a bone marrow-wide problem.
From there, your doctor may order additional tests depending on the suspected cause. Antibody testing can identify autoimmune destruction. Genetic testing can check for markers like the Duffy-null phenotype or gene mutations associated with blood cancers. A bone marrow biopsy, where a small sample of marrow is extracted and examined under a microscope, is sometimes necessary to evaluate how well the marrow is producing cells and whether abnormal cells are present. Vitamin levels, viral panels, and a thorough medication review round out the workup.
When Low Counts Become Dangerous
The primary risk of neutropenia is infection, and the danger scales with how low your count drops. At mild levels, most people function normally and may not even know their counts are low. At severe levels (below 500 cells per microliter), even bacteria that normally live harmlessly on your skin or in your gut can cause serious illness because there aren’t enough neutrophils to keep them in check.
A fever of 100.4°F (38.0°C) or higher in someone with known neutropenia is treated as a medical emergency, particularly for cancer patients on chemotherapy. Because neutrophils are responsible for the visible signs of infection like pus, redness, and swelling, a neutropenic person can have a serious infection with very subtle symptoms. Warning signs to watch for include shaking chills, a new cough or sore throat, burning during urination, worsening diarrhea, mouth sores or white patches on the gums, and any new redness or swelling around wounds or IV sites. These can escalate quickly without the immune firepower to contain them.