Background: Almost 60% of normal healthy term babies and 80% of preterm babies develop visible jaundice in the first week of life. Although the outcome of the majority is benign, newborns with untreated severe hyperbilirubinemia can develop short and long-term sequelae of bilirubin encephalopathy.Objectives: This study was designed to evaluate the impact of exchange transfusion on various biochemical parameters and to assess the need for routine calcium gluconate supplementation during the procedure. Methodology:We studied 84 newborn double volume exchange transfusions and recorded various biochemical parameters of sodium, potassium, calcium, ph and blood sugar during the procedure. Mostly fresh donor blood was employed for the procedures. Nearly 74% transfusions were performed with donor blood aged less than 2 days. Results:We observed no clinically significant alteration in recorded biochemical parameters during and after exchange transfusion. Routine intravenous calcium gluconate was not given to patients during the procedure. Though we observed a fall in serum calcium level during transfusion, but the concentrations remained within normal physiological range. Insignificant variation in recorded parameters and zero mortality were attributed to mostly using fresh blood for the exchange transfusions. Conclusion:We concluded that there was no significant alteration in serum electrolytes during and after exchange transfusion. Further, in contrast to the earlier reports of higher incidence of hyperkalemia during exchange transfusion, we observed a paradoxical fall in serum potassium during and after transfusion, although within normal range.