OBJECTIVE: The Life after Pediatric Sepsis Evaluation (LAPSE) investigation recently reported that one third of children who survive sepsis experience significant health-related quality of life (HRQL) impairment compared to baseline at one year after hospitalization. PERSEVERE is a multi-biomarker tool for estimating baseline risk of mortality among children with septic shock. We determined if the PERSEVERE biomarkers have predictive capacity for estimating the risk of hospital mortality and long-term HRQL morbidity among children with community-acquired septic shock. DESIGN: Secondary analysis. SETTING: Twelve academic pediatric intensive care units. PATIENTS: A subset of LAPSE subjects (n = 173) with available blood samples. INTERVENTIONS: None MEASUREMENTS AND MAIN RESULTS: Three predefined outcomes from the LAPSE investigation were evaluated: all-cause hospital mortality (n = 173), and the composite outcome of mortality or Persistent, Serious Deterioration of HRQL (PSD-HRQL; > 25% below baseline) among surviving children at 1 month (n = 125) or 3 months (n = 117). PERSEVERE had an AUROC of 0.73 (95% C.I. 0.59 to 0.87; p = 0.002) for estimating the risk of hospital mortality and was independently associated with increased odds of hospital mortality. In multivariable analyses, PERSEVERE was not independently associated with increased odds of the composite outcome of mortality or deterioration of PSD-HRQL > 25% below baseline. A new decision tree utilizing the PERSEVERE biomarkers had an AUROC of 0.87 (95% C.I. 0.80 to 0.95) for estimating the risk of PSD-HRQL at 3 months among children who survived septic shock. CONCLUSIONS: PERSEVERE had modest performance for estimating hospital mortality in an external cohort of children with community acquired septic shock. The PERSEVERE biomarkers appear to have utility for estimating the risk of PSD-HRQL up to three months after surviving septic shock. These findings suggest an opportunity to develop a clinical tool for early assignment of risk for long term HRQL morbidity among children who survive septic shock.