Background: Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by multiple auto-antibodies against self-directed antigens and multisystemic involvement. The SLE Disease Activity Index (SLEDAI-2K) scoring system evaluates the presence of multiple features of SLE flares at the time of completion or in the previous 10 days. Interleukin 37 (IL-37) is a newly defined member of cytokine family, and it is a key cytokine in regulating inflammation. Objectives: we aimed to detect the level of IL-37 in SLE and correlate it with the activity of disease. Methods: A cross sectional study included fifty children with SLE following up at the Pediatric Rheumatology Clinic, Specialized Children’s Hospital, Cairo University and chosen randomly; aged up to 16 years and thirty children will be assigned as the control group; with matched age and gender, apparently healthy children, with no family history or clinical manifestation suggestive SLE or any rheumatological disorders with history taken, full physical examination and routine labs including level of IL-37. Results: Levels of IL-37 in 50 cases with SLE have higher than in 30 controls but without statistically significant difference (P =0.08). Level of IL-37 in active cases with higher than in inactive cases but without statistically significant difference (P =0.58). Level of IL-37 level in mild activity with lower than in moderate or severe active but without statistically significant difference (P =0.23). Level of IL-37 is correlated with delay in diagnosis of disease and SLEDAI-2K score. Conclusion: level of IL-37 is higher in SLE patients than controls and it is higher in active cases than inactive cases. IL-37 is correlated with lag between onset and diagnosis of disease and SLEDAI-2K.