Background: Management of Systemic Lupus Erythematosus (SLE) would be greatly assisted by certain biomarkers that perfectly reflect changes in disease activity. Objectives: This study was conducted to evaluate the role of IL-17, IL-6 and their ratio in SLE as regard disease activity, central nervous system CNS and renal involvement. Methodology: A case control study including SLE patients were subjected to clinical examination, assessment of SLE disease activity index (SLEDAI) and laboratory investigations versus healthy controls, quantitative determination of serum IL-17A and IL-6 levels by ELISA. Results: Elevated serum IL-17A and IL-6 levels in SLE cases than control. Serum IL-6 level was higher in renal group, whereas, higher serum IL-17 was detected in neurologically affected patients. Conclusion: SLE patients had significantly upregulated IL-17 and IL-6 levels. SLEDAI was significantly positively correlated with IL-17/IL-6 ratio. Thus, IL-17/ IL-6 ratio may accurately characterize Th17-driven disease than serum IL-17 or IL-6 alone.