Traumatic brain injury (TBI) is the leading cause of mortality and disabilities among all trauma cases. Following TBI, damage to axons results in tau protein hyperphosphorylation leading to microtubule instability and tau-mediated neurodegeneration. In addition, tau protein is proteolytically cleaved and is able to access the cerebrospinal fluid (CSF) and serum; thus, this protein may serve as a potential biomarker in the diagnosis of injury severity and outcome prediction. Although a limited number of studies have investigated the CSF tau protein levels after TBI, the data are divergent and conflicting, and investigations into the serum tau protein levels have yet to be conducted. Therefore, the present study aimed to examine the serum tau protein levels in the full spectrum of TBI patients on days 0-14 after TBI, using an enzyme-linked immunosorbent assay. The protein levels were compared to the initial Glasgow Coma Score (GCS) and the Extended Glasgow Outcome Scale (GOS-E), which are used to represent the injury severity and patient outcome, respectively. In total, 56 patients, including 20 patients with mild TBI (GCS, 13-15), 19 patients with moderate TBI (GCS, 9-12) and 17 patients with severe TBI (GCS, 3-8), were included in the current study. The outcome was assessed 1 year after the injury and patients were classified into the good outcome (40 cases; GOS-E, 5-8) and poor outcome groups (16 cases; GOS-E, 1-4). The results indicated that serum tau protein levels increased soon after TBI and reached a peak value at similar to 2 days after the injury. The serum t protein levels were significantly higher in the severe TBI group compared with those in the mild and moderate TBI groups (P<0.0001). Univariate analysis indicated that poor outcome was significantly associated with higher serum tau protein levels on day 2 (P<0.0001). A receiver operating characteristic curve demonstrated that a tau protein level of >116.04 pg/ml on day 2 resulted in a 93.75% sensitivity and 92.50% specificity for predicting a poor outcome. Furthermore, a tau protein level of >372.1 pg/ml on day 2 yielded 100% sensitivity and 83.33% specificity for 1 year mortality in the severe TBI group. In conclusion, the present study suggests that serum tau protein may serve as a potential biomarker for evaluating the injury severity and predicting the outcome of TBI patients.