Maternal antibody production is stimulated when fetal red cells are positive for an antigen absent onmother's red cells. Alloimmune hemolytic disease of fetus and newborn due to anti E is uncommon. We report a case of anti-E hemolytic disease in a neonate who had severe fetal and mild neonatal hemolytic manifestations. The neonate was treated with phototherapy. He also received intravenous immunoglobulin and single PCV transfusion.