Aim:In critical diseases, immune-nutritional status plays an influential role in the clinical outcome. Studies have reported that the outcome of various diseases can accurately predicted using the Naples prognostic score (NPS) which is an immune-nutritional index, the. This study aimed to examine how NPS relates to 6-month outcomes in patients with severe traumatic brain injury (STBI).Material and Methods:We retrospectively analyzed the clinical data of 94 patients with STBI between September 2018 and September 2021. Galizia’s method was used to calculate NPS, and patients were categorized as high (NPS > 3) or low (NPS ≤ 3) NPS according to their NPS scores based on receiver operating characteristic curve analysis. In addition, the controlling nutritional status score (CONUT) and prognostic nutrition index (PNI) were calculated. Based on the modified Rank scale (mRS), the outcome for 6-months was evaluated. The mRS score for unfavorable outcomes was ≥ 3.Results:In the univariate analyses, patients in the unfavorable group had higher NPS scores (P < 0.001). The multivariate analysis demonstrated that NPS was an independent predictor of poor outcomes after adjusting for potential confounding factors (adjusted odds ratio = 7.463, 95% confidence interval [CI]: 1.131–49.253, P < 0.05). The area under the NPS curve for predicting poor outcomes was 0.755 (95% CI: 0.655–0.837, P < 0.001), which was significantly higher than Glasgow coma score (GCS), CONUT, and PNI (NPS vs. GCS, P = 0.013; NPS vs. CONUT, P = 0.029; NPS vs. PNI, P = 0.015).Conclusion:NPS can be considered to be a novel and better independent predictor of poor outcomes in patients with STBI.