OBJECTIVES: To evaluate the predictive ability of six severity assessment scoring systems, namely, Acute Physiology and Chronic Health Evaluation (APACHE II), Rapid Emergency Medicine Score (REMS), Sequential Organ Failure Assessment (SOFA), Multiple Organ Dysfunction Score (MODS), Predisposition, Infection, Response and Organ Dysfunction (PIRO) and Mortality in Emergency Department Sepsis (MEDS) scores, in patients with sepsis. METHODS: A prospective cohort study, carried out in a south Indian tertiary care teaching hospital. Institutional ethics committee approval was obtained prior to the study. All patients diagnosed with sepsis according to guidelines the third International Consensus Definitions for Sepsis and Septic shock (Sepsis 3), who meets the inclusion and exclusion criteria were enrolled into the study. Patients were followed from the day of admission to till the day of discharge or death. Patient demographics, clinical characteristics, laboratory test data and comorbidities were recorded on the day of sepsis diagnosis. These parameters were used to calculate the severity scores and predicted mortality for each patient. ROC curve analysis was used to analyse the discriminative power (ability to differentiate between survivors and non-survivors) of various severity scores. RESULTS: A total of 193 patients were included in the study. The mean age was 57.2±15.3 (mean±SD) years. Majority of the patients were male, 125 (64.76%). Overall mortality was 108 (55.9%). The calculated AUCs were 0.86 (95% CI: 0.80-0.90) for APACHE II, 0.81 (95% CI: 0.75-0.87) for REMS, 0.80 (95% CI: 0.74-0.86) for SOFA, 0.74 (95% CI: 0.67-0.80) for MODS, 0.78 (95% CI: 0.71-0.84) for PIRO and 0.77 (95% CI: 0.71-0.83) for MEDS. Sensitivity and specificity for APACHE II was 81.5 and 75.3 respectively. CONCLUSIONS: In our study, APACHE II score proved to be the most superior of all the scores, as it considers not only the laboratory data but also chronic comorbidities and surgical status of the patient.