Background:  Systemic lupus erythematosus (SLE) is a systemic illness marked by clinical variability, unpredictable outcome, and recurring flares. Interleukin 36α is crucial for innate immunity. It is strongly hypothesized that IL-36 has an impact on SLE pathogenesis. Aim: Assessing the link between interleukin 36α levels and disease activity in systemic lupus erythematosus (SLE). Subjects and Methods: This study examined forty systemic lupus erythematosus patients and 40 controls. The SLE disease activity index (SLEDAI) establishes disease activity. ELISA estimates serum Interleukin 36α.  Results: Interleukin 36 α levels were considerably higher in SLE patients compared with the controls (P < 0.001). IL-36α levels significantly linked to the SLE disease activity index (SLEDAI) score (P <0.001), age (P = 0.002), disease duration (P = 0.00), arthritis (P <0.001), nephritis (P = 0.002), and anti-double-stranded DNA antibody (P <0.001). IL-36 α levels and complement 3 were inversely linked (P < 0.001).  Conclusion: Interleukin 36α may identify SLE activity early in follow-up.