Background : Biomarker could be objective and reliable tools to predict mortality in sepsis. We explored the prognostic utilities of emerging biomarkers in septic patients and questioned whether adding biomarkers to the clinical variables would improve the prediction of mortality in sepsis. ; Methods : This retrospective study included 157 septic patients (112 patients with sepsis; 45 patients with septic shock). Procalcitonin (PCT), presepsin, galectin-3, and soluble suppression of tumorigenicity 2 (sST2) concentrations were analyzed in relation to the 30-day all-cause mortality. Their value added on top of Sequential (Sepsis-related) Organ Failure Assessment (SOFA) score, high-sensitivity C-reactive protein, and white blood cells was also analyzed. ; Results : PCT could not predict 30-day mortality. Univariate hazard ratio [HR with 95% confidence interval (CI)] of the other dichotomized variables was: 1.33 (0.55–3.194) for presepsin; 7.87 (2.29–26.96) for galectin-3; 1.55 (0.71–3.38) for sST2; and 2.18 (1.01–4.75) for SOFA score. The risk of 30-day mortality increased stepwise as the number of biomarkers above optimal cutoff values increased, and the highest risk was observed when all four biomarkers and SOFA score increased (HR = 14.5). Multi-marker approach predicted 30-day mortality better than SOFA score [area under the curves (95% CI), 0.769 (0.695–0.833) vs. 0.615 (0.535–0.692)]. In reclassification analyses, adding biomarkers to clinical variables improved the prediction of mortality. ; Conclusion : This study demonstrated a possible prognostic utility of PCT, presepsin, galectin-3, and sST2 in sepsis. Multi-marker approach could be beneficial for an optimized management of patients with sepsis.