A full term male infant was admitted to the neonatal intensive care unit due to jaundice and mild hemolytic anemia within the first 24 hours of his life. The total serum bilirubin level was 11.2 mg/dL at 24 hours of age. The patient was RhD positive and blood group A, and his mother was RhD positive and blood group B. The direct and indirect antiglobulin tests of the infant were all positive. On antibody screening and identification tests, anti-S antibodies were identified from both the infant and mother. The RBC phenotyping for S antigen revealed positive for infant and negative for mother. This report documents the first case of hemolytic disease of the fetus and newborn due to the anti-S antibody in Korea.