Objective: To evaluate the correlation between Acute Physiology and Chronic Health Evaluation II (APACHE II) score and plasma concentrations of copeptin, C-reactive protein (CRP) and procalcitonin in patients with sepsis. Methods: Patients with sepsis were prospectively enrolled. APACHE II scores were determined during the first 24 h after admission to the intensive care unit. Plasma copeptin, CRP and procalcitonin were quantified at admission, 24 h, 48 h, and 72 h. Survival at 28 days after admission was recorded. Results: APACHE II score was significantly positively correlated with plasma copeptin, CRP and procalcitonin concentrations. Survivors (n ¼ 15) had significantly lower APACHE II scores and copeptin, CRP and procalcitonin concentrations than nonsurvivors (n ¼ 26). APACHE II score, copeptin at 72 h, CRP at 48 h and procalcitonin at 24 h were independent risk factors for death. Conclusion: Plasma copeptin, CRP and procalcitonin concentrations were positively correlated with APACHE II score in patients with sepsis, and reflected disease severity.