What are the treatment recommendations for infectious mononucleosis (mono infection)?

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Last updated: December 29, 2025View editorial policy

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Treatment Recommendations for Infectious Mononucleosis

Treatment for infectious mononucleosis is entirely supportive, with no role for antiviral therapy in otherwise healthy individuals. 1

Core Treatment Principles

Supportive care is the mainstay of management, including adequate hydration, analgesics, antipyretics, and rest guided by the patient's energy level rather than enforced bed rest. 2, 3

Symptomatic Management

  • Analgesics and antipyretics (acetaminophen or NSAIDs) should be used for fever, headache, and pharyngeal pain relief. 2, 4
  • NSAIDs may provide particularly rapid symptom resolution in patients with atopic predispositions or enhanced immunological responses, with documented cases showing complete symptom improvement within hours of initiation. 5
  • Activity should be self-paced based on the patient's energy level; enforced bed rest is not recommended. 2

Medications NOT Routinely Recommended

  • Aciclovir (acyclovir) does not ameliorate the course of infectious mononucleosis in otherwise healthy individuals and should not be used. 1
  • Corticosteroids are NOT recommended for routine treatment and should be reserved exclusively for life-threatening complications. 1, 2, 6, 3

Corticosteroid Use: Specific Indications Only

Corticosteroids should be reserved ONLY for airway obstruction or severe pharyngeal edema causing respiratory compromise. 1, 2

  • Evidence from systematic review shows insufficient benefit for routine symptom control, with only transient improvement in sore throat at 12 hours that was not maintained. 6
  • Two trials found benefit at 12 hours (OR 21.00 for eight-day course; OR 4.20 for single dose), but this effect was not sustained beyond the initial period. 6
  • Potential adverse events including respiratory distress and acute onset of diabetes have been documented, though causality is uncertain. 6

Activity Restrictions and Return to Sports

Patients must avoid contact sports or strenuous exercise for at least 3-4 weeks from symptom onset to prevent splenic rupture, the most feared complication occurring in 0.1-0.5% of cases. 2, 4, 3

  • Current guidelines recommend 3 weeks of athletic restriction from onset of symptoms. 3
  • Some sources recommend extending this to 4 weeks or until splenomegaly resolves. 2, 4
  • Shared decision-making should determine the exact timing of return to activity, balancing the risk of splenic rupture against the patient's clinical status. 3

Special Populations: Immunocompromised Patients

In immunocompromised patients with suspected primary EBV infection, immunomodulator therapy should be reduced or discontinued if possible. 1

  • These patients have increased risk of EBV-associated lymphoproliferative disease and require specialist consultation. 1
  • Obtain complete blood count, blood film, and liver function tests in patients on immunosuppressive therapy with possible primary EBV infection. 1

Expected Clinical Course

  • Fatigue may persist for several months after acute infection resolves, though most symptoms resolve within 2-3 weeks. 2, 4
  • Infectious mononucleosis is a risk factor for chronic fatigue syndrome. 4
  • Most patients have an uneventful recovery with supportive care alone. 4, 3

Infection Control

Avoid sharing personal items contaminated with saliva and practice hand hygiene during outbreaks in close community settings, though precautions are generally not needed given the high seroprevalence of EBV. 1, 2

References

Guideline

Diagnosis and Treatment of Infectious Mononucleosis

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

Epstein-Barr virus infectious mononucleosis.

American family physician, 2004

Research

Infectious Mononucleosis: Rapid Evidence Review.

American family physician, 2023

Research

Infectious Mononucleosis: An Updated Review.

Current pediatric reviews, 2024

Research

Steroids for symptom control in infectious mononucleosis.

The Cochrane database of systematic reviews, 2015

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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