The increase in severe traumatic brain injury (sTBI) incidence is a worldwide phenomenon, resulting in a heavy disease burden in the public health systems, specifically in emerging countries. The shock index (SI) is a physiological parameter that indicates cardiovascular status and has been used as a tool to assess the presence and severity of shock, which is increased in sTBI. Considering the high mortality of sTBI, scrutinizing the predictive potential of SI and its variants is vital. To describe the predictive potential of SI and its variants in sTBI. This study included 71 patients (61 men and 10 women) divided into two groups: Survival (S; n = 49) and Non-survival (NS; n = 22). The responses of blood pressure and heart rate (HR) were collected at admission and 48 h after admission. The SI, reverse SI (rSI), rSI multiplied by the Glasgow Coma Score (rSIG), and Age multiplied SI (AgeSI) were calculated. Group comparisons included Shapiro-Wilk tests, and independent samples t-tests. For predictive analysis, logistic regression, receiver operator curves (ROC) curves, and area under the curve (AUC) measurements were performed. No significant differences between groups were identified for SI, rSI, or rSIG. The AgeSI was significantly higher in NS patients at 48 h following admission (S: 26.32 ± 14.2, and NS: 37.27 ± 17.8; P = 0.016). Both the logistic regression and the AUC following ROC curve analysis showed that only AgeSI at 48 h was capable of predicting sTBI outcomes. Although an altered balance between HR and blood pressure can provide insights into the adequacy of oxygen delivery to tissues and the overall cardiac function, only the AgeSI was a viable outcome-predictive tool in sTBI, warranting future research in different cohorts.