Background: Exchange transfusion (ET) is required in hospitalized hyperbilirubinemic neonates. Aims & Objectives: 1) To determine Baby‘s ABO blood group wise changes in haematological and biochemical parameters before, and after exchange transfusion .2) To study the effect of the whole blood exchange transfusion to decrease serum bilirubin and raise haemoglobin in neonatal hyperbilirubinemia. 3) To find out the underlying disease pattern of haemolytic jaundice among the study population. Materials & Methods: The study centre at SMS and associated hospitals. The blood bank is licensed and fully equipped. Fall in serum bilirubin minimum 40 cases was required as the sample size of the present study. Results: The distribution of blood groups B, O, A, and AB among the Neonates numbers was 21, 07, 10, and 2 respectively. When Neonate‘s blood group were A, B, AB and O then the Hb (g/dl), Haematocrit (%) and Direct bilirubin (mg/dl) mean values before, and after exchange transfusion was non–significant. When Neonate‘s blood group was B, AB and O then the Total bilirubin (mg/dl) and indirect bilirubin (mg/dl) mean values before, and after exchange transfusion was significant.