- Objectives: Sepsis remains a disease with a high mortality rate. The study goal was to assess long-term survival of severe sepsis in young patients. Design: Retrospective cohort study. Setting: Patients admitted with sepsis to ICUs in seven tertiary hospitals between 2003 and 2011. Patients: A total of 409 patients less than 45 years who survived to hospital discharge were age and sex matched with 818 patients with infectious disease without sepsis selected from internal medicine or surgical department admissions. Interventions: None. Measurements and main results: The median age in sepsis patients and the comparison group was 31 and 32 years, respectively. The proportions of patients surviving after hospital discharge were significantly lower in the sepsis group compared with the control group; among survivors, 6-month, 1-year, and 3-year mortality rates were 0.7% versus 0%, 4.5% versus 0.7%, 7.9% versus 1.2%, and 10.8% versus 1.8%, respectively (p < 0.001 for all). In a multivariate Cox proportional hazards regression model, sepsis was associated with an increased risk of mortality (hazard ratio, 3.79; 95% CI, 2.27-6.32), while controlling for age, Charlson Comorbidity Index, history of stroke, and congestive heart failure. Past the 24-month landmark, sepsis was not found to be an independent risk for mortality (hazard ratio, 1.79; 95% CI, 0.67-4.79). Based on cause of death analysis, chronic underlying comorbidities might explain the excess mortality in patients with sepsis. Conclusions: Young patients experiencing an episode of severe sepsis continue to be at higher risk of long-term mortality. The highest mortality rates were observed during the first 24 months following discharge.