AIM OF THE STUDY: 1. To estimate the levels of bilirubin and albumin in cord blood. 2. To estimate the relationship between cord blood bilirubin and occurrence of neonatal hyperbilirubinemia. 3. To estimate the relationship between cord blood albumin and occurrence of neonatal hyperbilirubinemia. METHODOLOGY: This prospective study was conducted in Rajah Mirasudhar Hospital, attached to Thanjavur Medical College, Thanjavur, during the period of Feburary 2017 to July2017. The study sample consisted of 55 healthy term newborn babies with blood group O +ve born to O +ve mothers as control and 37 healthy term newborns with blood group A +ve or B +ve born to O +ve mothers as case group. Umbilical cord blood was collected from newborns and serum albumin and bilirubin levels estimated. Relevant history was obtained from mother and maternal hospital records. The babies were followed-up daily for development of jaundice and serum bilirubin was measured in all newborns at 24 and 72 hours of life. RESULTS: 1. The mean serum total bilirubin in umbilical cord blood was 1.596+0.46 mg/dl in control group and 1.995+1.16 mg/dl in case group. 2. The umbilical cord serum albumin and total bilirubin correlates well with the development of significant neonatal hyperbilirubinemia requiring treatment in the form of phototherapy with or without exchange transfusion. 3. Umbilical cord serum albumin level of less than or equal to 3.15 g/dl predicts the development of significant hyperbilirubinemia with a sensitivity of 76.5%, specificity of 78.7% and an accuracy of 77.6%. The accuracy of prediction of significant hyperbilirubinemia by cord serum albumin is higher for babies with ABO incompatibility when compared with control group. 4. Umbilical cord serum total bilirubin of more than or equal to1.85 mg/dl predicts the development of significant hyperbilirubinemia with a sensitivity of 70.6%, specificity of 82.7% and an accuracy of 76.7%. CONCLUSION: 1. In ABO blood group incompatibility, neonates with umbilical cord blood total bilirubin >1.85 mg/dl and albumin 3.15 g/dl can be safely discharged early. 2. Hence, we recommend routine measurement of serum bilirubin and albumin levels in umbilical cord blood at birth to predict those newborns at risk of developing significant hyperbilirubinemia requiring treatment in the form of phototherapy with or without exchange transfusion.