Background. The objective of this study was to assess the correlation between sepsis, obesity, and mortality of patients admitted to an Intensive Care Unit (ICU). Subjects and Methods. Data of all patients admitted to the ICU of a tertiary hospital during a 28-month period were retrospectively analyzed and included in the study. Results. Of 834 patients included, 163 (19.5%) were obese, while 25 (3.0%) were morbidly obese. Number of comorbidities (P < 0.001), bloodstream infection (P 0.033), and carbapenemase-producing Klebsiella pneumoniae colonization during ICU stay (P 0.005) were significantly associated with obesity, while nonobese patients suffered more frequently from spontaneous intracranial hemorrhage (P 0.038). Total ICU mortality was 22.5%. Increased mortality among obese ICU patients was observed. Sepsis was the main condition of admission for which obese patients had statistically lower survival than normal weight subjects (76.3% versus 43.7%; P 0.001). Mortality of septic patients upon admission was independently associated with SOFA score upon ICU admission (P 0.003), obesity (P 0.014), pneumonia (P 0.038), and development of septic shock (P 0.015). Conclusions. Our study revealed that sepsis upon ICU admission is adversely influenced by obesity but further studies are needed in order to assess the role of obesity in sepsis outcome.