Traumatic brain injury (TBI) represents a pressing challenge in emergency medicine due to its high mortality rates and profound impact on patients' lives. Neuron-specific enolase (NSE) levels have emerged as a promising biomarker for assessing TBI severity and prognosis, offering valuable information to guide clinical decision-making in emergency departments. Aim: The aim of this literature review is to evaluate the comparison of Neuron Specific Enolase (NSE) levels in serum and cerebrospinal fluid in patients with severe traumatic brain injury. Material and Methods: The research method used involves identifying the research objective to evaluate the difference in NSE levels between serum and cerebrospinal fluid in patients with severe traumatic brain injury, selecting clear inclusion and exclusion criteria, searching the literature using relevant keywords in medical databases, extracting data from studies that meet the inclusion criteria, analyzing the data to identify patterns and differences in NSE levels, preparing a research report that includes an introduction, methods, results, and conclusions based on the findings from the literature review, as well as presenting information systematically and comprehensively according to scientific writing standards. Results: The results of the literature review discussion indicate a significant difference in NSE levels between serum and cerebrospinal fluid in patients with severe traumatic brain injury, with potential implications for the diagnosis and prognosis of traumatic brain injury. Conclusion: The comparison of Neuron Specific Enolase (NSE) levels in serum and cerebrospinal fluid among patients with severe traumatic brain injury reveals a significant divergence, suggesting NSE's potential as a diagnostic and prognostic biomarker.