Abstract: Background: The cause for disease and mortality throughout the infant was hypoxic ischemical encephalopathy secondary to perinatal asphyxia. It leads to permanent neuropsychological disability. Identification of a biomarker for hypoxic insult can not only help in earlier implementation of neuro-protective strategies but also in prognosticating the long term outcome. Method: A prospective observational study conducted in IMS and SUM hospital over a period of 2 years in which 60 newborns with clinical evidence of HIE were recruited as case group. A group of 20 newborns with no evidence of HIE served as control. The serum neuron specific enolase (NSE ) levels at 4hours and 48 hours of birth of both the groups were tested and compared. Results: The mean serum NSE levels at 4hours and 48 hours was significantly higher in the case group ( 42.43 ng/ml, 28.97 ng/ml) as compared to the control group (18.51ng/ml, 15.62ng/ml). Additionally, the mean serum NSE stages increased by the harshness of HIE in the various subgroups as per the clinical staging. ROC curve for this study has shown a good predictability for neurological outcome. For the cut off value of 40.4 mcg/l, the sensitivity was 80 % and specificity was 81.2 %. Conclusion: Serum NSE levels can be a reliable biomarker for neurological insult in Hypoxic ischemic Encephalopathy insult in order to implement early neuroprotective strategy