Abstract: Objective To explore the diagnostic value of interleukin (IL)-6, IL-10, and procalcitonin (PCT) in patients with severe abdominal infections due to bacterial pathogens. Methods A total of 1 993 hospitalized patients with ascitic fluid culture-positive results at the Affiliated Hospital of Xuzhou Medical University from January 2020 to December 2022 were enrolled and their clinical data were retrospectively analyzed. After medical record review, 549 clinical cases of patients diagnosed with severe abdominal infections were selected. These cases were divided into two groups based on the causative pathogens: a Gram-positive (G⁺) bacteria group (n=245) and a Gram-negative (G^-) bacteria group (n=304). Their differences in IL-6, IL-10, and PCT levels were analyzed, and the diagnostic value for identifying pathogens was evaluated. Results The area under the ROC curve (AUC) for predicting G^- positive bacteria using IL-6, IL-10, PCT, or their combination was 0.851, 0.835, 0.769, and 0.904, respectively (all P<0.05). The threshold for predicting G^- positive bacteria with IL-6 was 176.32 ng/L, with a sensitivity of 72.2% and a specificity of 87.5%; for IL-10, the threshold was 4.71 ng/L, with a sensitivity of 69.4% and specificity of 84.5%; for PCT, the threshold was 3.03 μg/L, with a sensitivity of 67.3% and specificity of 74.7%. The combined prediction of G^- positive bacteria had a sensitivity of 91.4% and specificity of 78.9%. Levels below these thresholds suggested a higher possibility of G⁺ bacterial infections. Conclusions IL-6, IL-10, and PCT can be used to differentiate between early G^- and G⁺ bacterial infections in patients with severe abdominal infections. Combined prediction offers higher sensitivity and may help guide the early selection of appropriate antimicrobial therapy in clinical practice.