OBJECTIVES: Sepsis-3 criteria define sepsis as ≥2 points rise of Sequential Organ Failure Assessment (SOFA) score, either from zero or a known baseline. We compared the efficacies of quick Sequential Organ Failure Assessment (qSOFA), SOFA, and Systemic Inflammatory Response Syndrome (SIRS) scores to predict sepsis mortality. METHODS: Prospective, hospital-based study was undertaken to determine the efficacies of various sepsis-scoring systems to predict mortality in sepsis. The "Sepsis-2" criteria of "severe sepsis" and "septic shock" were used as selection criteria as they correspond to "sepsis" and "septic shock" of "Sepsis-3". Statistical analysis was done by SPSS Statistics version-16. Mortality predictions were made using receiver operator characteristic curve testing. RESULTS: We included 122 sepsis patients diagnosed by "Sepsis-2" definition; 78.68% (n = 98) of whom met "Sepsis-3" criteria for sepsis. All-cause mortality was 50%. On univariate analysis, we found age over 60 years [odds ratio (OR) = 4.244, 95% confidence interval (CI) = 1.309-13.764, p = 0.016], invasive mechanical ventilation (OR = 7.0076, 95% CI = 3.053-16.0809, p<0.0001), and presence of acute respiratory distress syndrome (ARDS) (OR = 2.757, 95% CI = 1.0091-7.535, p = 0.048) were significant predictors of mortality. The SOFA score yielded the best result with "area under the curve" (AUC) of "receiver operating characteristic" (ROC) curve of 0.868. On comparing AUCs between these scores difference between both SOFA and qSOFA was highly significant (p < 0.0001) compared to SIRS. However, such statistical difference was not found between AUCs of SOFA and qSOFA. CONCLUSIONS: Both SOFA and qSOFA are superior prognostication tools compared to SIRS to predict sepsis mortality; SOFA being better than qSOFA.