BACKGROUND: Traumatic brain injury (TBI) is a common public health problem. Mild TBI is any head injury with Glasgow Coma Scale (GCS) above 12. TBI comes to the forensic team's attention. Computed tomography (CT) is the investigation of choice in head injury being available relatively cheap and rapidly acquainted but less than 1 percent of head trauma patients have findings on CT brain and it does not predict the neuropsychiatric outcome of the mild TBI patients. Failure of diagnosis of head trauma patients and its management might be well-thought-out as a medicolegal negligence against the doctors. Biomarkers were proved to increase in brain insults such as strokes or even in trauma cases not involve head injuries. OBJECTIVES: The aim of this study was to assess how serum NSE and S100B, correlated to functional outcome and to compare the sensitivity and specificity of the 2 biomarkers in order to minimize the risk of medicolegal liabilities against the doctors and hospitals. PATIENTS AND METHODS: 50 patients with the diagnosis of mild TBI admitted to the ER of Benha University Hospital were enrolled, CT brain, serum levels of S100 – β and NSE were detected. Meanwhile, 50 non trauma persons were enrolled and have the same managements. The present investigation was carried out with consent from Benha faculty of medicine research ethics committee (Rc: 35-5-2023). Written informed consent was obtained from all subjects or their legally authorized representatives prior to starting the study. RESULTS: Serum levels of S100 and NSE were noted to be elevated in trauma patients compared to the control group. CONCLUSIONS: S100 protein is more sensitive and specific than NSE as prognostic biomarker for the long-term outcome of mild head trauma and may serve as potential targets for treatment.