Sepsis and septic shock are among mortality causes following major surgeries. The Charlson co-morbidity index consists of 19 weighted categories related to chronic health which measures the burden of co-morbidity. The goal of this study was to determine the incidence of postoperative sepsis in patients underwent gynecological and gastrointestinal cancer surgeries and predictive role of Charlson index for this situation. Two hundred and twenty-two patients who underwent gynecological and gastrointestinal cancer surgeries were evaluated. Sixty-four (28.6%) patients developed SIRS postoperatively. Forty-four (19.7%) patients developed sepsis postoperatively. Mean age, duration of hospitalization and surgery, the Charlson score were significantly higher in patients who developed sepsis than other cases. Blood transfusion and Charlson score were independent predictors of sepsis occurrence. Charlson co-morbidity index is a predictive factor for developing postoperative sepsis.