AbstractNecrotizing soft tissue infections (NSTI) have a 90-day mortality rate of 18–22%. Tools are needed for estimating the prognosis and severity of NSTI upon admission. We evaluated soluble urokinase-type plasminogen activator receptor (suPAR) levels at admission as a prognostic marker of NSTI severity and mortality. In a prospective, observational cohort study, suPAR was measured in 200 NSTI patients. We compared admission suPAR levels in survivors and non-survivors, patients with septic shock and non-shock, amputation and non-amputation, correlations with Simplified Acute Physiology Score II (SAPS II) and the Sequential Organ Failure Assessment (SOFA) score. Admission suPAR levels were higher in septic shock vs. non-septic shock patients (9.2 vs. 5.8 ng/mL, p-value < 0.001) and non-survivors vs. survivors (11 vs. 6.1 ng/mL, p-value < 0.001) and correlated with SAPS II (r = 0.52, p < 0.001) and SOFA score (r = 0.64, p < 0.001). Elevated suPAR upon admission was associated with 90-day mortality (log-rank test p < 0.001), however not after adjustment for age, sex, and SOFA score. The AUC for suPAR and 90-day mortality was 0.77. We found that suPAR is a promising candidate for prognosis and severity in patients with NSTI.