BACKGROUND Serum albumin and prealbumin are both negative acute-phase reactants, and usually at low levels in stress. We aim to determine their predictive values for poor outcome of traumatic brain injury (TBI). METHODS A total of 326 patients of TBI were enrolled and followed-up by telephone 6 months after discharge. They were divided into a favorable group (GOS: 3 to 5) and an unfavorable group (GOS: 1 to 2). Serum albumin and prealbumin were measured from vein blood within 24 h after admission. RESULTS Ninety one (27.9%) patients were with poor outcome (GOS: 1 to 2). The unfavorable group had lower albumin and prealbumin (P<0.001). Albumin and prealbumin were both positively correlated with GCS (r = 0.489, P<0.001; r = 0.222, P<0.001, respectively) and GOS (r = 0.518, P<0.001; r = 0.314, P<0.001, respectively). After adjustment for confounding factors, the odds ratios of albumin and prealbumin were 0.866, 95% CI: 0.829 to 0.904 and 0.990, 95% CI: 0.985 to 0.995, respectively. In subgroup of GCS≤8 (n = 101), the crude and adjusted odds ratios of serum albumin were both statistically significant (P = 0.027, P = 0.033, respectively), while prealbumin were not (P = 0.553, P = 0.576, respectively). The AUC of albumin for predicting poor outcome was 0.762, 95% CI: 0.712 to 0.807, which was significantly higher than that of prealbumin (0.664, 95% CI: 0.610 to 0.715). In analyses of all patients and subgroup of GCS≤8, the AUCs of serum albumin were both significantly higher than those of prealbumin (P = 0.001, P = 0.045, respectively). CONCLUSIONS Both serum albumin and prealbumin could predict the poor outcome of TBI, but the former is much better, especially, in patients with severe TBI.