Introduction: Neuron-specific enolase (NSE) is a sensitive marker of brain injury after hypoxia or ischemia. There are few studies about its usefulness in asphyxiated newborns. Objective: This work aims to asses if NSE can be a serum biochemical marker of brain damage in the newborn after perinatal asphyxia and to study the correlation between serum NSE levels and neurological outcome in newborns with hypoxic-ischemic encephalopathy. Patients And Methods: We have determined the blood values of NSE by Enzyme immunometric assay using Enzyme immunometric assay kit in 30 asphyxiated term-newborns with clinical encephalopathy (of mild, moderate and severe degree) and in 20 healthy term-newborns (control group). Blood samples were obtained within the first 48 hours after birth in all neonates. Results: The mean serum NSE of HIE group (69.5 µg/L) was significantly higher than control group (18.6 µg/L). Meanwhile, serum NSE concentrations were significantly higher in grade III encephalopathy compared to grade II and I where it was 130.3 µg/L, 72.9 µg/L and 28.2 µg/L in the three subgroups respectively. A significant positive correlation was found between NSE and umbilical artery base deficit in the asphyxiated group. Apgar score at 10 minutes was highly predictive for moderate HIE and serum NSE concentration was also highly predictive for severe HIE. Conclusion: Our results do not confirm serum NSE as an early predictor of HIE nor a good predictor for moderate HIE but it is highly predictive for sever HIE and for poor outcome.