Background: Severe traumatic brain injury (TBI) remains associated with high in-hospital mortality. Although classical clinical predictors are widely used, additional biomarkers reflecting systemic dysfunction may improve prognostic assessment. Small intestinal bacterial overgrowth (SIBO) may represent a late marker of critical illness. This study evaluated the prognostic value of SIBO compared with traditional predic-tors in severe TBI. Methods: In this retrospective cohort study, 174 patients with severe TBI (Glasgow Coma Scale ≤ 8) were included. Baseline clinical parameters were rec-orded at admission. Quantitative cultures of small intestinal aspirates were obtained at admission (colony-forming units per milliliter, CFU/mL; CFU1) and on days 12–14 (CFU14). Multivariable logistic regression, receiver operating characteristic (ROC), and landmark analyses were performed. Results: Age (OR 1.06 per year, 95% CI 1.03–1.10, p < 0.001), lower GCS (OR 0.48 per point, 95% CI 0.28–0.83, p = 0.008), and res-piratory dysfunction reflected by lower PaO₂/FiO₂ values independently predicted mortality. Late bacterial load >10⁵ CFU/mL showed a strong association with death (OR 5.15, 95% CI 2.15–12.34, p < 0.001). Baseline CFU1 was not significant. The model demonstrated good discrimination (AUC = 0.84). Landmark analysis confirmed higher post-day-14 mortality and delayed discharge with elevated CFU14. Conclusions: Late intestinal bacterial overgrowth is independently associated with mortality and may complement traditional predictors for risk stratification in severe TBI.