Objective To investigate the value of Charlson’s weighted index of comorbidities (WIC) in predicting the prognosis of patients with sepsis. Methods The clinical data of 234 septic patients in the last three years were retrospectively analyzed. The scores of WIC and acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ ) were calculated. The patients were divided into two groups according to death or survival outcome 28 days later, and the value of WIC score in predicting prognosis was analyzed. Results It was found that 77 (32.9%) of the 234 patients died. Increasing WIC score was associated with increased mortality. Multiple logistic regression analysis revealed that WIC was a risk factor of prognosis of septic patients (OR=1.434, 95% CI:1.097-1.875, P=0.008). The areas under the ROC curves in predicting the mortality of the septic patients were 0.670 (0.591-0.748) for the WIC score, 0.770(0.703-0.837) for APACHEⅡ score and 0.821 (0.757-0.885) for the combination of both. Conclusion WIC score can satisfactorily predict the influence of underlying diseases on the prognosis of septic patients.