Context: In recent years, in addition to neurological and neuroradiologic examinations, attempts have been made to assess the severity of post-traumatic brain injury and to obtain an early idea of patient prognosis using biochemical markers with a high degree of brain tissue specificity. One such enzyme is neuron-specific enolase (NSE). Objective: to Investigate the serum levels of neuron specific enolase (NSE) in patients with head injury and correlate them with their outcome and other clinical parameters. Methods: twenty patients with brain injury were included in this prospective study. Neurologic examination and CT-scan were performed. NSE was measured on admission and after 48h by using nonisotopic sandwich immunoassays. Results: a significant difference between NSE serum concentration and the two groups—minor head injuries and severe head injuries (7.1±4.8 versus17.2±13.5; p= 0.04). A statistically significant correlation was observed between an increase of NSE serum values and a cerebral pathological finding in CT scans (p=0.04).NSE levels were significantly higher in patients who died or had a poor outcome than in those who were alive or had good outcome (30±14 versus10.2 ± 9.3; p=0.01). The area under the curve (AUC) for NSE prediction of poor vs. good outcome was 0.76. A serum NSE level of 7.9µg/L was 85% sensitive and 77% specific in predicting poor outcome. Serum level of NSE at 18µg/L can detect mortality by 100% sensitivity and 90% specificity. Conclusion: serum neuron specific enolase levels after head injury may be a useful marker to predict extent of the brain damage and the outcome.