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Source of infection is an independent predictor of sepsis-related mortality. To date, studies have failed to evaluate differences in septic patients based on the source of infection.Retrospective study of all patients with sepsis admitted to the ICU of a university hospital within a 12 month time period.Sepsis due to intravascular device and multiple sources had the highest number of positive blood cultures and microbiology whereas lung and abdominal sepsis had the least. The observed hospital mortality was highest for sepsis due to multiple sources and unknown cause, and was lowest when due to abdominal, genitourinary (GU) or skin/soft tissue. Patients with sepsis due to lungs, unknown and multiple sources had the highest rates of multi-organ failure, whereas those with sepsis due to GU and skin/soft tissue had the lowest rates. Those with multisource sepsis had a significantly higher median ICU length of stay and hospital cost.There are significant differences in patient characteristics, microbiology positivity, organs affected, mortality, length of stay and cost based on the source of sepsis. These differences should be considered in future studies to be able to deliver personalized care.Sepsis due to IVD/multiple sources has the highest number of positive cultures.Hospital mortality was highest for sepsis due to multiple sources and unknown cause.Sepsis due to lungs/unknown/multiple sources has highest multi-organ failure rates.Multisource sepsis has higher ICU length of stay and hospital cost.Differences between sources should be considered to deliver personalized care.