5 Most Common Reasons for Low White Blood Cell Count (Leukopenia)

Leukopenia — a white blood cell count below the normal range (typically below 4,000 cells per microliter in adults) — is not a diagnosis itself but a finding that points toward an underlying cause. White blood cells are produced in the bone marrow and have a lifespan of a few days; any process that suppresses production or accelerates destruction can produce a low count. The five causes below account for the vast majority of cases.

A single low white blood cell count reading is often transient and may not require treatment. Persistent leukopenia, or a count that is significantly below normal, warrants medical evaluation to identify the underlying cause.

1. Viral Infections

The most common cause of a temporarily low white blood cell count in otherwise healthy people is a viral infection. Certain viruses directly attack white blood cells or suppress the bone marrow’s production of them. Influenza, COVID-19, HIV, hepatitis, Epstein-Barr virus (which causes mononucleosis), and other viral infections are all associated with leukopenia during the acute phase of illness.

The mechanism varies by virus. HIV specifically targets and destroys CD4+ T-cells (a type of white blood cell), making the count a key marker of disease progression. Most other viral causes produce a temporary suppression that resolves as the infection clears. In a routine blood test during or immediately after a significant viral illness, a low white blood cell count often requires no specific treatment beyond monitoring.

2. Medications

Several classes of medication suppress white blood cell production as a known side effect. Chemotherapy agents are the most commonly associated — they work by targeting rapidly dividing cells, which includes both cancer cells and the bone marrow cells that produce white blood cells. This is why oncology patients require regular blood count monitoring.

Beyond chemotherapy, other medications with documented associations with leukopenia include:

• Certain antipsychotics, particularly clozapine (which carries a specific risk of agranulocytosis — severe reduction of a specific white blood cell type)
• Some anticonvulsants
• Certain antibiotics, including trimethoprim-sulfamethoxazole (Bactrim)
• Immunosuppressive drugs used for organ transplant and autoimmune conditions
• Some antithyroid medications

Anyone experiencing unexplained leukopenia who takes medications in these categories should have a discussion with their prescribing physician about whether the medication is the cause.

3. Bone Marrow Disorders

White blood cells are produced in the bone marrow. Conditions that affect the bone marrow’s ability to produce blood cells affect all blood cell types, including white blood cells. Aplastic anemia — in which the bone marrow fails to produce sufficient blood cells — is one of the more serious causes of leukopenia. Myelodysplastic syndromes (MDS), which involve abnormal bone marrow function, also commonly produce low white blood cell counts.

Certain blood cancers — including some leukemias — can paradoxically produce leukopenia when the bone marrow is so occupied with producing abnormal cells that normal white blood cell production is crowded out. Bone marrow disorders as a cause of leukopenia typically require a bone marrow biopsy for definitive diagnosis and often warrant referral to a hematologist.

4. Autoimmune Conditions

Some autoimmune diseases cause the immune system to destroy the body’s own white blood cells or the bone marrow cells that produce them. Systemic lupus erythematosus (lupus) is one of the most commonly associated — leukopenia is actually one of the diagnostic criteria for lupus. Rheumatoid arthritis, Sjögren’s syndrome, and certain other autoimmune conditions are also associated with white blood cell suppression.

The mechanism in autoimmune leukopenia is the production of antibodies against white blood cells or their precursors — the immune system targeting itself. Treatment focuses on managing the underlying autoimmune condition, which typically improves the white blood cell count as the autoimmune activity is controlled.

5. Nutritional Deficiencies

Deficiencies in specific nutrients required for white blood cell production can produce leukopenia. Vitamin B12 and folate (folic acid) deficiencies are the most commonly associated — both are essential for DNA synthesis in blood cell production, and their deficiency produces a condition called megaloblastic anemia that also affects white blood cell counts. Copper deficiency, while less common, can also impair bone marrow function.

These nutritional causes are particularly relevant in people with restrictive diets, malabsorption conditions (such as Crohn’s disease or celiac disease), bariatric surgery history, or limited dietary variety. B12 deficiency is also common in strict vegans who do not supplement, as B12 is found primarily in animal-derived foods.

Nutritional causes of leukopenia are among the most straightforward to treat — supplementation typically produces improvement within weeks — but require a blood test to confirm the deficiency and appropriate supplementation to correct it.

If a low white blood cell count is found on a routine blood test, the next step is typically a repeat test to confirm the finding, followed by investigation into the most likely cause based on the patient’s medical history, medications, and symptoms.