Interleukin-10 (IL-10) presents a dual role in systemic lupus erythematosus (SLE), illustrating pro-inflammatory and anti-inflammatory effects. This study addressed the possible associations between serum IL-10 levels and demographic characteristics, laboratory parameters, organ manifestations, disease activity, and treatment response in SLE patients. A total of 88 SLE patients from the Rheumatology Clinic of the Clinical Rehabilitation Hospital, Iași, were enrolled. Disease activity was assessed using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Serum cytokine levels were measured using an enzyme-linked immunosorbent assay (ELISA). Serum IL-10 levels were significantly higher in males compared to females (47.62 pg/mL vs. 13.24 pg/mL, p = 0.011) but not significantly associated with age or disease duration. However, IL-10 showed positive correlations with inflammatory markers and autoantibodies, including C-reactive protein (p = 0.002), IL-6 (p = 0.01), ANA (p = 0.