The impact of infectious source on sepsis outcomes for surgical patients is unclear. The objective of this study was to evaluate the association between sepsis sources and cumulative 90-d mortality in patients admitted to the surgical intensive care unit (SICU) with sepsis. All patients admitted to the SICU at an academic institution who met sepsis criteria (2014-2019, n = 1296) were retrospectively reviewed. Classification of source was accomplished through a chart review and included respiratory (RT, n = 144), intra-abdominal (IA, n = 859), skin and soft tissue (SST, n = 215), and urologic (UR, n = 78). Demographics, comorbidities, and clinical presentation were compared. Outcomes included 90-d mortality, respiratory and renal failure, length of stay, and discharge disposition. Cox-proportional regression was used to model predictors of mortality; P < 0.05 was significant. Patients with SST were younger, more likely to be diabetic and obese, but had the lowest total comorbidities. Median admission sequential organ failure assessment scores were highest for IA and STT and lowest in urologic infections. Cumulative 90-d mortality was highest for IA and RT (35% and 33%, respectively) and lowest for SST (20%) and UR (8%) (P < 0.005). Compared to the other categories, UR infections had the lowest SICU length of stay and the highest discharge-to-home (57%, P < 0.0005). Urologic infections remained an independent negative predictor of 90-d mortality (odds ratio 0.14, 95% confidence interval: 0.1-0.4), after controlling for sequential organ failure assessment. Urologic infections remained an independent negative predictor of 90-d mortality when compared to other sources of sepsis. Characterization of sepsis source revealed distinct populations and clinical courses, highlighting the importance of understanding different sepsis phenotypes. [ABSTRACT FROM AUTHOR]