Red blood cell (RBC) alloimmunization which is the production of antibodies in response to foreign red cell antigen(s) may occur through exposure to cells or tissues from a genetically different member of same species via transfusion, transplantation or pregnancy.It may cause hemolytic disease of fetus and newborn (HDFN). Usually the incidence of HDFN due to irregular erythrocyte antibody is rare in primigravida. Here we report a primigravida pregnant woman who developed multiple alloantibodies and the neonate developed severe HDFN.A 36-year-old primigravida pregnant woman whohad no history of significant medical issues except surgery done for severe endometriosis 1 year back and she had no history of previous blood transfusion presented to us for delivery.The antibody screening came out to be positive with a reaction in cell I and cell II of the antibody screening panel. Further, a mixture of anti D + anti C + anti E alloantibodies were identified using 16 cells panel, select cells and red cell phenotyping. The neonate developed severe HDFN which was managed with phototherapy, exchange transfusion and IvIg. There was no exposure history for sensitization except bleeding in early 2nd trimester.There was a significant discrepancy among mother, father and neonate Rh phenotype which was resolved with clinical history of Invitro fertilization (IVF) with sperm donation. This index case illustrates the need of antibody screening in primigravida antenatal women specially for Rh D negative high risk cases. It also shows importance of Rh Kell typing in sperm donors for future transfusion support of the child.