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The purpose of the study was to quantify the ability of procalcitonin (PCT) and interleukin-6 (IL-6) to differentiate noninfectious systemic inflammatory response syndrome (SIRS) and sepsis and to predict hospital mortality.We recruited consecutively adult patients with SIRS admitted to an intensive care unit. They were divided into sepsis and noninfectious SIRS based on clinical assessment with or without positive cultures. Concentrations of PCT and IL-6 were measured daily over the first 3 days.A total of 239 patients were recruited, 164 (68.6%) had sepsis, and 68 (28.5%) died in hospital. The PCT levels were higher in sepsis compared with noninfectious SIRS throughout the 3-day period (P < .0001). On admission, PCT concentration was diagnostic of sepsis (area under the curve of 0.63 [0.55–0.71]), and IL-6 was predictive of mortality, (area under the curve of 0.70 [0.62–0.78]). Peak IL-6 concentration improved the risk assessment of Sequential Organ Failure Assessment (SOFA) score for prediction of mortality among those who went on to die by an average of 5% and who did not die by 2%Procalcitonin measured on intensive care unit admission was diagnostic of sepsis, and IL-6 was predictive of mortality. Addition of IL-6 concentration to SOFA score improved risk assessment for prediction of mortality. Future studies should include clinical indices, for example, SOFA score, for prognostic evaluation of biomarkers.