Although antibodies to antigens in the Rh blood group system are common causes of warm autoimmune hemolytic anemia, specificity for only the D antigen is rare in autoimmune hemolysis in pediatric patients. This case reports an anti-D associated with severe hemolytic anemia (Hb = 2.1 g/dL) in a previously healthy 14-month-old child who presented with a 3-day history of low-grade fevers and vomiting. Because of his severe anemia, on admission to the hospital he was found to have altered mental status, metabolic acidosis, abnormal liver function tests, and a severe coagulopathy. He was successfully resuscitated with uncrossmatched units of group O, D- blood, and after corticosteroid therapy he had complete resolution of his anti-D-mediated hemolysis.