Background: Sepsis is a complicated clinical syndrome resulting from inflammatory reactions to bacteria or their products. IL-6 is a potent inflammatory cytokine produced by many cells, such as leucocytes, monocytes, endothelial cells, and fibroblasts. IL-6 plays an important role in the immune response and inflammation reactions regulation. Objective: the present study aimed to detect if IL-6 serum level and polymorphism correlate with severity of sepsis. Methodology: The study includes 70 subjects, 50 patients (Case) were chosen with at least 2 SIRS criteria and 20 healthy who were age matched. The patients were categorized into systemic inflammatory response syndrome (SIRS), sepsis, severe sepsis, septic shock and multi-organ dysfunction syndrome (MODS) according to ACCP/SCCM. Bactec Culture on automated blood culture system (Bact/ALERT 3D) was used as a gold standard method to prove sepsis . Serum IL-6 was measured by Enzyme linked immunosorbent assay (ELISA). Genotyping of the IL-6–174 G/C promoter polymorphism was performed using restriction fragment length polymorphism (RFLP) analysis. Results: Our study reported a statistically high significant difference of the IL-6 values between the case and control groups where p