Background: Sepsis is a life-threatening condition characterized by a dysregulated host response to infection. Early diagnosis and risk stratification are crucial for improving patient outcomes. This study aimed to evaluate the diagnostic and prognostic utility of biomarkers in critically ill patients with sepsis.Methods: In this prospective observational study, 160 patients (120 with sepsis, 40 with non-infectious SIRS) admitted to the ICU were included. Levels of procalcitonin (PCT), C-reactive protein (CRP), interleukin-6 (IL-6), soluble triggering receptor expressed on myeloid cells-1 (sTREM-1), and lactate were measured within 24 hours of ICU admission. The diagnostic and prognostic performance of biomarkers was evaluated using receiver operating characteristic (ROC) curve analysis and logistic regression.Results: PCT, IL6, and lactate demonstrated good diagnostic performance in differentiating sepsis from non-infectious SIRS, with AUCs of 0.88, 0.82, and 0.75, respectively. The combination of PCT, CRP, and IL-6 yielded an AUC of 0.92. Lactate, IL-6, and PCT were strong predictors of 28-day mortality (AUCs: 0.80, 0.78, and 0.75, respectively), organ dysfunction, and ICU length of stay. The sepsis group had significantly higher SOFA scores at day 7 (median 6 vs. 3, p<0.001) and longer ICU stay (median 12 days vs. 7 days, p<0.001) compared to the non-infectious SIRS group.Conclusions: Biomarkers, particularly PCT, IL-6, and lactate, have good diagnostic and prognostic utility in the management of sepsis in critically ill patients. The use of biomarker panels may further improve diagnostic accuracy and prognostic performance. These findings support the incorporation of biomarkers into clinical decision-making to facilitate early recognition and risk stratification of sepsis in the ICU setting.