Multisystem inflammatory syndrome of children (MIS-C) is a clinical picture that entered the medical nomenclature after the coronavirus disease 2019 pandemic. Although it primarily affects older children, there have been a limited number of cases reported during the neonatal period. Herein we present a patient, a late preterm infant, with severe MIS-C-related cerebral sinus venous thrombosis who was successfully treated with therapeutic plasma exchange. Practitioners can consider therapeutic plasma exchange as a safe and effective option for the treatment of critically ill MIS-C cases.