Introduction: Sepsis is one of the most important causes of mortality in the intensive care setting. An effective predictor of prognosis of sepsis is required to assess morbidity and mortality of this condition. In this study, sepsis in the intensive care unit (ICU) of a tertiary care hospital was evaluated, with specific reference to clinical features and causative organisms. The sequential organ failure assessment (SOFA) score was calculated to assess the severity of sepsis and multi-organ failure at presentation and after 48 h. The correlation of SOFA and mean SOFA scores with outcome was studied. Materials and Methods: This was a prospective, observational, cohort study carried out in a tertiary care teaching hospital. Forty consecutive cases of septicemia were studied. Detailed history, clinical features, and SOFA score was recorded to assess the disease severity at the time of presentation and after 48 h. Inclusion of patients in the study was performed using the American College of Chest Physicians/Society of Critical Care Medicine (ACCP/SCCM) defi nition of sepsis. Two sample t-test and 95% confi dence interval (CI) for difference of mean was applied. Results: When the SOFA score was <7, the mortality was 56%. It increased to 70% when the score was 8-15 (P = 0.0989, t value: 1.69, Mean difference: 2.12, 95% CI: 0.41-4.665). Patients with SOFA score <7 after 48 h had 52% mortality and it increased to 88% when the score was 8-15. The mean SOFA score at 48 h was 6.96 in patients who died and 2.5 in those who improved (P < 0.001, t value: 4.332, mean difference: 4.39, 95% CI: 2.34-6.44). Hence, the predictive value for mortality of SOFA score was better at 48 h than at presentation. Conclusions: Sequential assessment of organ dysfunction in ICU at presentation and at 48 h is a good indicator of prognosis. Both mean and highest SOFA scores are particularly useful predictors of outcome, independent of the initial score. A high SOFA score at 48 h of presentation predicts an increased mortality rate.