Hemolytic disease in a newborn that causes early jaundice is common. It is often due to the Rh (D) and ABO incompatibility, but rarely due to unexpected antibodies. Among these unexpected antibodies, the anti-Di(a) antibody rarely occurs. The anti-Di(a) antibody was observed in the serum and red-cell eluate of an infant, and in the serum of his mother. The frequency of the appearance of the Di(a) antigen in the Korean population is estimated to be 6.4-14.5%. This paper reports a case of hemolytic disease in a newborn associated with the anti-Di(a) antibody. A full-term male infant was transferred to the authors' hospital due to hyperbilirubinemia the day after his birth. The laboratory data indicated a hemoglobin value of 11.6 g/dL, a reticulocyte count of 10.6%, a total bilirubin count of 14.4 mg/dL, a direct bilirubin count of 0.6 mg/dL, and a positive result in the direct Coombs' test. Due to the identification of an irregular antibody from the maternal serum, an anti-Di(a) antibody was detected, which was also found in the eluate made from the infant's blood. The infant had been treated with phototherapy and intravenous immunoglobulin since the second day after his birth and was discharged due to an improved condition without exchange transfusion. Therefore, in cases of iso-immune hemolytic disease in a newborn within 24 hours from birth who had a negative result in an antibody screening test, the conduct of an anti-Di(a) antibody identification test is recommended due to the suspicion of an anti-Di(a) antigen, followed by early administration of intravenous immunoglobulin.