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Infectious mononucleosis secondary to Epstein-Barr virus typically follows a relatively benign and self-limited course. A small subset of individuals may develop further progression of disease including hematologic, neurologic, and cardiac abnormalities. A mild transient neutropenia occurring during the first weeks of acute infection is a common finding however in rare cases a more profound neutropenia and agranulocytosis may occur up to 6 weeks following the onset of initial symptoms. We describe the case of an 18-year-old woman who presented 26 days following an acute infectious mononucleosis diagnosis with agranulocytosis and fever. No source of infection was identified and the patient had rapid improvement in her symptoms and resolution of her neutropenia. The presence of fever recurrence and other non-specific symptoms in individuals 2–6 weeks following acute infectious mononucleosis symptom onset may warrant further assessment for this uncommon event.