Lymphocytosis: What it is, Causes, Signs, Symptoms & Treatment

GetWellGo explains lymphocytosis: causes, symptoms & treatments. Global healthcare support for international patients seeking trusted medical help.

Lymphocytosis: What it is, Causes, Signs, Symptoms & Treatment

  • Category

    General

  • Published By

    GetWellGo Team

  • Updated on

    12-Jun-2025

What causes lymphocytosis?

Lymphocytosis is an elevation of the number of lymphocytes (one of the white blood cells) in the blood. Lymphocytes play a critical role in the immune system and consist of T cells, B cells, and natural killer (NK) cells.

Causes of Lymphocytosis

Lymphocytosis can be categorized as either:

  • Reactive (secondary) – secondary to infections or other non-cancerous causes
  • Clonal (primary) – secondary to cancers of the blood or disorders of the bone marrow

Infections (Most frequent cause)

Viral Infections:

  • Epstein-Barr virus (EBV) – Infectious mononucleosis
  • Cytomegalovirus (CMV)
  • Hepatitis viruses
  • HIV (early stages)
  • Varicella-zoster virus
  • Mumps, measles, rubella

Bacterial Infections:

  • Pertussis (whooping cough)
  • Tuberculosis
  • Brucellosis

Parasitic Infections:

  • Toxoplasmosis
  • Malaria

Chronic Inflammatory Conditions

  • Autoimmune diseases (e.g., rheumatoid arthritis, Graves' disease)
  • Inflammatory bowel disease

Hematologic Malignancies (Clonal Lymphocytosis)

  • Chronic lymphocytic leukemia (CLL) – most common adult leukemia
  • Acute lymphoblastic leukemia (ALL) – more prevalent in children
  • Lymphomas (particularly those spilling into the blood)
  • Hairy cell leukemia

Stress-Related or Physiologic Causes

  • Acute physical/emotional stress
  • Post-surgery or trauma
  • After intense exercise

Smoking

  • Persistent lymphocytosis is commonly found in chronic smokers.

Drug responses

  • Lymphocytosis is sometimes caused by drugs (e.g., phenytoin).

Post-splenectomy

  • Spleen removal can result in mild persistent lymphocytosis.

Lymphocytosis symptoms

If due to a Viral or Bacterial Infection

  • Fever
  • Fatigue
  • Sore throat
  • Swollen lymph nodes (especially in the neck)
  • Runny nose or cough
  • Muscle aches
  • Enlarged spleen or liver (e.g., in EBV infections)

If due to Hematologic Cancer (like CLL or ALL)

  • Persistent fatigue
  • Unexplained weight loss
  • Night sweats
  • Fever without infection
  • Painless swollen lymph nodes
  • Easy bruising or bleeding
  • Frequent infections
  • Bone pain (especially in acute leukemia)

If due to Autoimmune Disease

  • Joint pain or swelling
  • Rashes
  • Dry eyes or mouth
  • General inflammation signs

Is lymphocytosis cancer?

Lymphocytosis is not necessarily cancer, but cancer can cause it in certain situations.

When Lymphocytosis is not Cancer:

In most individuals, particularly children and young adults, lymphocytosis is reactive — that is, it's due to the body's normal reaction to:

  • Viral infections (such as Epstein-Barr virus, influenza, COVID-19)
  • Bacterial infections (such as pertussis, tuberculosis)
  • Inflammatory or autoimmune conditions
  • Stress or smoking
  • This type of lymphocytosis is temporary and typically clears once the underlying condition is treated or resolves.

When Lymphocytosis may be a Sign of Cancer:

Lymphocytosis may be a manifestation of blood cancers that include lymphocytes, namely:

  • Chronic Lymphocytic Leukemia (CLL)
  • Most often in adults aged 60 and above
  • Causes chronic high levels of lymphocytes for months
  • Often with no initial symptoms, or with fatigue, enlarged lymph nodes, or infections

Acute Lymphoblastic Leukemia (ALL)

  • More common in children
  • Rapid onset with extremely elevated white cell counts
  • Symptoms: tiredness, bruising, pyrexia, bone ache

Other Lymphoid Cancers

  • Some lymphomas can present with lymphocytosis when malignant lymphocytes leak into the blood

Red Flags That Suggest Cancer

  • Lymphocytosis that persists longer than 2 months
  • Extremely elevated lymphocyte level (most often > 5,000–10,000 cells/μL)
  • Presence of abnormal (atypical or immature-appearing) lymphocytes in the blood

Association with:

  • Night sweats
  • Weight loss
  • Unexplained fever
  • Enlarged lymph nodes or spleen

Treatment for lymphocytosis

Treatment for lymphocytosis relies solely on its cause. Lymphocytosis is not a disease but a symptom that the immune system is responding to something — an infection, inflammation, or in some cases a cancer.

If Due to an Infection (Most Common Cause)

  • No treatment for the lymphocytosis itself
  • The body typically normalizes lymphocyte levels after an infection resolves.

Viral Infections (e.g., EBV, CMV, influenza):

  • Rest, hydration, control of fever
  • No antiviral medications unless severe (e.g., HIV)

Bacterial Infections (e.g., pertussis, tuberculosis):

  • Antibiotics as indicated
  • Lymphocyte count typically returns to normal in weeks following resolution of infection.

If Due to Hematologic Cancer (e.g., CLL, ALL, lymphoma)

  • Clonal lymphocytosis requires targeted therapy

Chronic Lymphocytic Leukemia (CLL):

  • Typically monitored (watchful waiting) if asymptomatic

Treatment options (if required):

  • Targeted therapies (e.g., ibrutinib, venetoclax)
  • Immunotherapy
  • Chemotherapy (less frequently now)

Acute Lymphoblastic Leukemia (ALL):

  • Requires prompt treatment
  • Chemotherapy
  • Stem cell transplant in high-risk

Lymphoma-associated lymphocytosis:

  • Managed according to lymphoma type and stage

If Due to Autoimmune Disease or Chronic Inflammation

  • Treat the underlying autoimmune disease (e.g., lupus, rheumatoid arthritis)
  • Corticosteroids
  • Immunosuppressants

If Due to Physiologic or Temporary Causes

Stress-associated or smoking-associated lymphocytosis:

  • Treatment not necessary
  • Will resolve by stress management or smoking cessation

Post-splenectomy lymphocytosis:

  • Mild, chronic lymphocytosis is normal
  • No treatment necessary

Signs of lymphocytosis in adults

Viral Infection–Related Lymphocytosis

  • Fatigue or malaise
  • Fever
  • Sore throat
  • Swollen lymph nodes (especially in the neck)
  • Runny nose, cough
  • Enlarged spleen or liver (especially with EBV)

Bacterial Infection (e.g., Pertussis, TB)

  • Persistent cough (often whooping-type in pertussis)
  • Fever and chills
  • Night sweats
  • Weight loss (common in tuberculosis)

Hematologic Cancers (e.g., CLL, ALL, Lymphoma)

These cancers can cause persistent or unexplained lymphocytosis, often with systemic symptoms:

Red Flag Symptoms in Adults:

  • Unexplained weight loss
  • Persistent fatigue
  • Night sweats
  • Fever without infection
  • Painless, swollen lymph nodes (neck, armpits, groin)
  • Frequent infections
  • Enlarged spleen or liver
  • Bruising or bleeding easily (especially in leukemia)

Autoimmune or Inflammatory Conditions

  • Joint pain or swelling
  • Skin rashes
  • Mouth ulcers
  • Dry eyes/mouth (e.g., in Sjögren's syndrome)
  • Generalized inflammation signs

Other Signs (Less Common Causes)

  • Post-splenectomy: mild persistent lymphocytosis without symptoms
  • Stress or Smoking: usually asymptomatic and found incidentally

Lymphocytosis in children causes

Lymphocytosis in children — increased numbers of lymphocytes in the blood — is normal and harmless, particularly when caused by infections. It does, however, on occasion, signal more severe conditions such as leukemia.

Common Causes:

Viral Infections (most common cause)

Children's immune systems tend to react vigorously to viruses with elevated lymphocytes.

Examples:

  • Epstein-Barr virus (EBV) – mononucleosis
  • Cytomegalovirus (CMV)
  • Adenovirus
  • Measles
  • Mumps
  • Rubella
  • Influenza
  • Hepatitis viruses
  • COVID-19

Bacterial Infections (less common)

Some bacterial infections, especially chronic or atypical infections, are responsible for causing lymphocytosis.

Examples:

  • Pertussis (whooping cough) – classically associated with significant lymphocytosis
  • Tuberculosis (TB)

Hematologic Malignancies

Recurrent or extremely high lymphocyte counts may be suspicious for childhood leukemia.

Examples:

  • Acute lymphoblastic leukemia (ALL) – most common childhood cancer
  • Chronic lymphocytic leukemia (CLL) – unusual in children
  • Consider fatigue, bruising, infections, weight loss, or swollen lymph nodes.

Autoimmune or Inflammatory Conditions

Less common in children, but could occur.

Examples:

  • Juvenile idiopathic arthritis
  • Lupus (SLE)
  • Sarcoidosis

Other Causes

  • Post-splenectomy (following spleen removal)
  • Stress response (physical/emotional stress)
  • Smoking exposure (in teens or older children)

Lymphocytosis and viral infection

Lymphocytosis — a rise in the number of lymphocytes (a form of white blood cell) in the blood — is most often caused by viral infections, particularly among children and young adults. It's typically a normal reaction to infection and will often clear up once the infection has passed.

Why Do Viral Infections Cause Lymphocytosis?

  • Lymphocytes (predominantly T cells, B cells, and NK cells) are the body's first line of immune defense against viruses.
  • Once a virus enters the body, it triggers both the bone marrow and lymphoid tissues to make and release additional lymphocytes into the circulatory system.
  • This can result in reactive (or benign) lymphocytosis.

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