Background: IL-18 can modulate both innate and adaptive immunity and its dysregulation can cause autoimmune or inflammatory diseases. IL-35 is related to occurrence and progression of a variety of diseases; it is mainly involved in immune response, autoimmune diseases, infections and inflammation, as a new inflammatory factor, IL 35 can be used as a promising therapeutic target. This study aimed to detect the value of IL-18 and IL 35 in the serum of patients of bacterial infection with or without sepsis and evaluate prognostic value of IL-18 and IL-35 in bacterial infection with or without sepsis. Methods: This prospective study was done on 70 patients admitted by bacterial infection. Patients were divided into two equal groups: Group 1: Bacterial Infection with Sepsis and group 2: Bacterial Infection without Sepsis. Results: Significant differences were noted between studied groups regarding IL-18 and IL-35 (p=0.001 and 0.012 respectively). Significant differences were noted between studied groups regarding APACHE Score, SOFA Score and prognosis (p=0.001). In both group: There was negative correlation between IL-18 and IL-35. Conclusion: The elevation of IL-18 supports its role in diagnosing and monitoring sepsis, while the decrease of IL-35 may indicate a failure of anti-inflammatory responses during septic conditions. Serum IL-18 is a superior biomarker for predicting sepsis compared to serum IL-35, demonstrating higher sensitivity and accuracy. While IL-35 may still provide some utility in clinical settings, its lower diagnostic performance suggests it should not be relied upon as the primary marker for sepsis detection.