While antiseizure medications (ASMs) exhibit the ability to influence the immune system, the specific immunosuppressive consequences in neonates remain insufficiently delineated. Levetiracetam is regarded a safe and effective second-line treatment following phenobarbital, particularly in cases where first-line agents are ineffective or result in adverse reactions in neonatal seizures. We present a neonate who developed B-cell lymphopenia due to levetiracetam administration, which constitutes a previously unrecognized adverse effect of the medication in neonates. To our knowledge, this case marks the initial documented occurrence of B-cell lymphopenia associated with levetiracetam in a neonate.