Abstract Background Translocator protein (TP) is related to inflammation and is involved in brain injury. The objective of this study was to ascertain whether serum TP concentrations are associated with the severity and prognosis of traumatic brain injury (TBI). Methods We quantified the serum concentrations of TP in 106 healthy controls and 106 patients with severe TBI. Recorded prognostic variables included acute lung injury, acute traumatic coagulopathy, progressive hemorrhagic injury, posttraumatic cerebral infarction, 6-month mortality and 6-month poor outcome (Glasgow Outcome Scale score of 1–3). Trauma severity was assessed by Glasgow coma scale (GCS) score. Extent of inflammatory response was indicated by serum interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-a) and C-reactive protein (CRP) concentrations. Results Patients had significantly higher serum TP concentrations than controls. Among patients, serum TP concentrations strongly and independently correlated with GCS score and serum IL-6, TNF-a and CRP concentrations. Serum TP was identified as an independent predictor for the preceding prognostic variables, its prognostic predictive ability was similar to that of GCS score and it also significantly improved prognostic predictive ability of GCS score. Conclusion Serum TP may be intimately linked with in inflammation, disease progression and poor prognosis in TBI patients. Highlights • Significant elevation of serum translocator protein levels after head trauma. • Intimate relation of serum translocator protein levels to trauma severity. • Emergence of serum translocator protein as a determinant for poor prognosis. • Identification of serum translocator protein with a high prognostic discriminatory ability. [ABSTRACT FROM AUTHOR]