Bupropion is not a well established cause of medication-induced pancytopenia. In this report, we discuss a case of agranulocytosis, normocytic anemia and severe thrombocytopenia, with concurrent drug-induced rash within 3 weeks of bupropion initiation. Bone marrow biopsy demonstrated hypocellularity <10% without dysplastic features or increase in blast cells. Other causes of cytopenias, including infections, nutritional deficiencies, autoimmune disorders, liver/renal disease, thrombotic microangiopathy, primary bone marrow disorders and secondary marrow infiltrative diseases were ruled out. Pancytopenia resolved after 1 week of bupropion discontinuation and supportive care.