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Introduction: The pathophysiology of sepsis consists of two phases. A first phase characterized by a substantial increase of pro-inflammatory mediators including cytokines and systemic inflammatory markers, and a second phase (immunoparalysis, immunodysregulation) associated with the rise of anti-inflammatory mediators. In this study we prospectively analyzed 52 consecutive patients with diagnosis of systemic inflammatory response syndrome (SIRS) at hospital admission to evaluate prognostic and early diagnostic performance of interleukin-10 (IL-10), soluble CD25 (sCD25) and interferon-γ (IFN-γ) and to confirm the prognostic accuracy of the sequential organ failure assessment (SOFA) score., Methods: Patients were divided in two groups (group 1, n=28 patients with bacteremic SIRS and group 2, n=24 patients with non-bacteremic SIRS) and then stratified into survivors (n=39) and nonsurvivors (n=13). Serum markers were evaluated on the day of hospital admission (D-1) and on the 7th day of hospital stay (D-7). Concentration of sCD25 was evaluated by a sandwich ELISA kit. Levels of IL-10 and IFN-γ were quantified by a cytokine biochip array by the evidence investigator analyzer. Differences between groups were established by the Mann-Whitney test. Accuracy, sensitivity and specificity of diagnostic markers were evaluated by the receiver-operating characteristic curve analysis. Multivariate analysis was carried out to evaluate whether studied biomarkers are independent predictors of poor outcome in prognosis, and of bacteremic SIRS in diagnosis., Results: IL-10, sCD25 and SOFA scores of survivors and nonsurvivors were significantly different both at D-1 (P=0.0014; P=0.014 and P=0.0311 respectively) and at D-7 (P=0.0002, P=0.014 and P=0.0012 respectively). Between the above groups IFN-γ level was significantly different only at D-7 (P=0.0013). Moreover IL-10 and sCD25 were significantly higher in bacteremic versus non-bacteremic SIRS patients at D-1 and at D-7 (P<0.05). IFN-γ values showed a significant decrease (P<0.05) in patients of group 1 only at D-7. The diagnostic accuracy of IL-10 and sCD25 was confirmed by the analysis of the AUROCC at D-1 and D-7 respectively. Multivariate analysis revealed that sCD25 and IL-10 are independent predictors of a poor outcome for our patients during the first day of hospital admission., Conclusions: IL-10 and sCD25 gave a significant contribution to prognostic evaluation and early diagnosis of bacteremic SIRS. SOFA score appeared to be a reliable prognostic tool in this subset of patients.