Introduction: Jaundice is most common problem faced by neonates in the first week of life. Although physiological jaundice is more frequent as compared to pathological jaundice, so it is very important to differentiate between the two as pathological jaundice may lead to kernicterus and subsequently brain damage. There are various modalities of investigations for diagnosis of jaundice e.g. complete blood count, Total serum bilirubin, Blood group, Direct and Indirect coomb's test, G-6PD deficiency etc. by which we can reach at diagnosis. Treatment is also dependent upon the amount of total serum bilirubin and various other laboratory investigations. Thus laboratory workup is very important for diagnosis, prevention of neonatal hyperbilirubinemia and its complications. With this background present study was conducted for the analysis of clinicopathological profile among infants with neonatal hyperbilirubinemia. Aims and Objectives: The current study was planned to assess the hematological profile of neonatal jaundice and to categorize it on the basis of causes and severity. Materials and Methods: The present study conducted on 140 neonates admitted in NICU, at tertiary care centre, Ahmedabad; during first week of life along with total serum bilirubin level greater than 5 mg/dl. Peripheral blood was drawn from all study subjects under aseptic precautions and study done for Total Serum bilirubin, Direct and indirect coomb's test, Blood group, G-6PD deficiency, complete blood count and CRP. Results: In our study among 140 cases with neonatal jaundice, Total number of Pre-term babies (< 37 weeks) was 91 (65%). Most of the neonates were present with jaundice at the age of 2-4 days. Physiological jaundice constituted majority in 95 cases (67%). ABO incompatibility was the commonest cause of pathological jaundice followed by septicemia. The rise in total serum bilirubin level was found to be more in pathological jaundice as compare to physiological jaundice.