Although delayed hemolytic transfusion reaction (DHTR) has been widely recognized as a serious complication of red blood cell transfusion in patients with sickle cell disease (SCD), there is no consensus on its optimal management. Discontinuation of transfusion is recommended, whereas corticosteroids and immunoglobulins are considered to be beneficial. We report 2 children with sickle cell anemia who were diagnosed with DHTR and experienced a subsequent neurologic event in the course of treatment with corticosteroids. The role of corticosteroids as possible precipitating factors of neurologic complications is discussed. Pending a better understanding of the chain of events of DHTR, SCD children with DHTR should receive steroids with great caution.