Aims:To investigate initial Sequential Organ Failure Assessment (SOFA) score of patients in Intensive Care Unit (ICU), who were diagnosed with infectious disease, as an indicator of multiple organ dysfunction and to examine if initial SOFA score is a better mortality predictor compared to Simplified Acute Physiology Score (SAPS).Materials and Methods:Hospital-based study done in medical ICU, from June to September 2014 with a sample size of 48. Patients aged 18 years and above, diagnosed with infectious disease were included. Patients with history of chronic illness (renal/hepatic/pulmonary/  cardiovascular), diabetes, hypertension, chronic obstructive pulmonary disease, heart disease, those on immunosuppressive therapy/chemoradiotherapy for malignancy and patients in immunocompromised state were excluded. Blood investigations were obtained. Six organ dysfunctions were assessed using initial SOFA score and graded from 0 to 4. SAPS was calculated as the sum of points assigned to each of the 17 variables (12 physiological, age, type of admission, and three underlying diseases). The outcome measure was survival status at ICU discharge.Results:We categorized infectious diseases into dengue fever, leptospirosis, malaria, respiratory tract infections, and others which included undiagnosed febrile illness, meningitis, urinary tract infection and gastroenteritis. Initial SOFA score was both sensitive and specific; SAPS lacked sensitivity. We found no significant association between age and survival status. Both SAPS and initial SOFA score were found to be statistically significant as mortality predictors. There is significant association of initial SOFA score in analyzing organ dysfunction in infectious diseases (P < 0.001). SAPS showed no statistical significance. There was statistically significant (P = 0.015) percentage of nonsurvivors with moderate and severe dysfunction, based on SOFA score. Nonsurvivors had higher SAPS but was not statistically significant (P = 0.094).Conclusions:Initial SOFA score is a superior mortality predictor. It easily measures degree of organ dysfunction in infectious diseases and complements other scoring systems.