A low white blood cell count, called leukopenia, happens when your blood contains fewer than 4,500 white blood cells per microliter. The causes range from temporary and easily fixable (a viral infection, a medication side effect) to chronic conditions that need ongoing management. Understanding the most common reasons can help you make sense of an unexpected lab result.
White blood cells can drop for two basic reasons: your bone marrow isn’t producing enough of them, or something is destroying them faster than they can be replaced. Sometimes both are happening at once.
Infections That Lower Your Count
It seems counterintuitive that an infection would lower the very cells your body uses to fight it, but certain viruses do exactly that. HIV is the most well-known example. It directly kills a specific type of white blood cell (CD4+ T cells), and somewhere between 49% and 65% of people with advanced HIV infection show depleted levels of these cells. The virus also damages the thymus and bone marrow, organs responsible for producing new white blood cells.
Other viruses that can cause low counts include hepatitis C, Epstein-Barr virus, and SARS-CoV-2 (the virus behind COVID-19). These infections lower white blood cells through several overlapping mechanisms: triggering the cells to self-destruct, flooding the body with inflammatory signals that disrupt new cell production, and in some cases directly infecting the stem cells in bone marrow that give rise to white blood cells. The drop is usually temporary and recovers as the infection clears, though HIV requires treatment to restore counts.
Medications and Drug Reactions
Dozens of common, non-chemotherapy medications can lower white blood cells as a side effect. The drugs most frequently linked to this problem include:
- Anti-thyroid medications used to treat overactive thyroid (Graves’ disease), including propylthiouracil, carbimazole, and methimazole. Roughly 0.2% to 0.5% of people taking these drugs develop significantly low counts.
- Clozapine, an antipsychotic used for treatment-resistant schizophrenia, which causes low white blood cells in about 1% of users. This is why people on clozapine get regular blood monitoring.
- Certain antibiotics, particularly amoxicillin, cotrimoxazole (Bactrim), vancomycin, and several penicillin-type drugs.
- Sulfasalazine, used for inflammatory bowel disease and rheumatoid arthritis.
In most drug-induced cases, the immune system creates antibodies that mistakenly target and destroy white blood cells. The count typically recovers after the medication is stopped, though the timeline varies.
Cancer Treatments
Chemotherapy and radiation therapy are among the most predictable causes of low white blood cells. Blood cell production is one of the most sensitive processes in the body to both radiation and chemotherapy drugs, because bone marrow cells divide rapidly, and these treatments target rapidly dividing cells without distinguishing cancerous ones from healthy ones.
In studies of breast cancer patients treated with common chemotherapy regimens, 87.5% developed low white blood cell counts, and nearly a third dropped to severely low levels. Radiation therapy has a particular impact on lymphocytes, a subset of white blood cells. Patients receiving radiation to the head, chest, or pelvis saw their lymphocyte counts drop by 51% to 68% from baseline by the end of treatment. After treatment stops, counts can begin recovering within one to two weeks, though full recovery takes longer depending on the type and intensity of therapy.
Autoimmune Diseases
When the immune system turns on itself, white blood cells can become collateral damage. In autoimmune neutropenia, the body produces antibodies that specifically target and destroy neutrophils, the most abundant type of white blood cell and the one most critical for fighting bacterial infections.
This can happen on its own (primary autoimmune neutropenia, most common in young children and often self-resolving) or as a complication of another autoimmune condition. Lupus and rheumatoid arthritis are the diseases most frequently associated with secondary autoimmune neutropenia. Autoimmune hemolytic anemia can also drive the count down.
Bone Marrow Disorders
Since the bone marrow is the factory where white blood cells are made, any disease that damages or crowds out normal marrow tissue can lead to low counts. Aplastic anemia is one of the most serious examples. In this condition, the bone marrow fails to produce enough of all blood cell types, including white blood cells, red blood cells, and platelets.
Leukemia and other blood cancers can also cause leukopenia, even though they involve the overproduction of abnormal white blood cells. The abnormal cells take over marrow space and prevent the development of functional, mature white blood cells. Myelodysplastic syndromes, a group of conditions where the marrow produces defective blood cells, work in a similar way. Myelofibrosis, where scar tissue replaces healthy marrow, is another cause.
Nutritional Deficiencies
Your bone marrow needs specific nutrients to manufacture white blood cells, and running short on them can cause counts to fall. The most important ones are vitamin B12, folate, and copper.
Vitamin B12 deficiency is the most common nutritional cause. It leads to a condition called megaloblastic anemia, where the marrow produces oversized, dysfunctional blood cells. The good news is that supplementation works quickly. In documented cases, neutrophil counts normalized within 7 to 10 days after B12 replacement began. Copper deficiency causes a similar pattern of low white blood cells and anemia, and can even mimic myelodysplastic syndrome on bone marrow examination, potentially leading to misdiagnosis. Copper-related neutropenia can begin improving within just 3 days of supplementation.
These deficiencies are particularly worth considering because they’re treatable and sometimes overlooked. People who’ve had weight-loss surgery, follow very restrictive diets, or have conditions that impair nutrient absorption are at higher risk.
Genetic Conditions
Some people are born with gene mutations that affect how neutrophils develop, survive, or function. These congenital neutropenia syndromes, sometimes called Kostmann disease or severe congenital neutropenia, are rare but can cause persistently low counts from infancy. Researchers have identified mutations in at least nine genes linked to these syndromes, though in some affected individuals the specific mutation remains unknown. These conditions typically require lifelong management with medications that stimulate white blood cell production.
An Enlarged Spleen
The spleen filters blood and removes old or damaged cells. When it becomes enlarged (a condition called hypersplenism), it traps and destroys white blood cells faster than normal. This can result from liver disease, certain infections, or blood cancers. The spleen essentially becomes overactive, pulling too many healthy cells out of circulation.
How Low Counts Are Investigated
If a routine blood test reveals a low white blood cell count, the first step is usually a detailed breakdown of which types of white blood cells are low. A drop in neutrophils points toward different causes than a drop in lymphocytes. Your doctor will typically start with your medical history and a physical exam, which in most cases narrow down the likely explanation.
From there, selective lab tests can check for infections, nutritional deficiencies, or autoimmune markers. A peripheral blood smear, where a technician examines your blood cells under a microscope, can reveal abnormal cell shapes that suggest specific conditions. If the cause remains unclear, a bone marrow biopsy may be recommended to look directly at how your marrow is producing cells. Additional cultures of blood, urine, or other samples may be taken if infection is suspected.
What Low White Blood Cells Feel Like
A mildly low count often produces no symptoms at all. Many people only discover it through routine bloodwork. When counts drop significantly and stay low over time, the main consequence is increased vulnerability to infections. You might notice that you catch colds or other illnesses more often, that minor cuts or scrapes take longer to heal, or that you develop fevers without an obvious cause. Mouth sores, skin infections, and persistent fatigue are also common signs that your immune defenses are compromised.
A single low reading doesn’t necessarily signal a serious problem. Temporary dips happen with common viral illnesses and often resolve on their own. Persistently low counts, or counts that are dropping over time, warrant a closer look to identify and address the underlying cause.