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Background: Although sepsis is one of the leading causes of mortality in hospitalized patients, information regarding early predictive factors for mortality and morbidity is limited. Materials and Methods: Patients fulfilling the Infectious Disease Society of America criteria of sepsis within the medical intensive care unit (ICU) were included over two years. Apart from baseline hematological, biochemical, and metabolic parameters, Acute Physiology and Chronic Health Evaluation II (APACHE II), Simplified Acute Physiology Score II and III (SAPS II and SAPS III), and Sequential Organ Function Assessment (SOFA) scores were calculated on day 1 of admission. Patients were followed till death or discharge from the ICU. Results: One hundred patients were enrolled over two years (54% males). The overall mortality was 53%, (69.5% in females, 38.8% in males (P < 0.01). Mortality was 65.7%, 55.7%, and 33.3% in patients with septic shock, severe sepsis, and sepsis, respectively. Patients who died were significantly older than the survivors (mean age, 57.37 ± 20.42 years and 44.29 ± 15.53 years respectively, P < 0.01). Nonsurvivors were significantly more anemic and had higher APACHE II, SAPS II, SAPS III, and SOFA scores. The presence of acute respiratory distress syndrome and renal dysfunction were associated with higher mortality (75% and 70.2%, respectively). There was no significant difference in the duration of mechanical ventilation or ICU stay between survivors and nonsurvivors. On multivariate analysis, significant predictors of mortality with odds ratio greater than 2 included the presence of anemia, SAPS II score greater than 35, SAPS III score greater than 47, and SOFA score greater than 6 at day 1 of admission. Conclusion: Several demographic and laboratory parameters as well as composite critical illness scoring systems are reliable early predictors of mortality in sepsis. A sepsis mortality prediction formula (AIIMS Sepsis Score) based on SAPS II, SAPS III, and SOFA scores and hemoglobin has greater predictive power than these scoring methods individually. Routine use of critical illness scoring systems and a composite mortality prediction formula may provide useful early prognostic information in sepsis/severe sepsis. [ABSTRACT FROM AUTHOR]