Levetiracetam (LEV) is a second-generation antiepileptic drug approved for the treatment of several types of epilepsy. We report a 45-year-old female who developed hypogammaglobulinemia and B cell aplasia during LEV treatment. The Naranjo probability score for an adverse drug reaction was 6. After LEV discontinuation, the number of B cells gradually increased and reached normal levels within two months. This case suggests that monitoring of immunoglobulin levels and lymphocyte subsets analysis is important in patients treated with LEV, especially in cases of prolonged infections.