Interleukin 10 (IL-10) plays a role in inflammation and cell-type responses. The anti-SS-A/Ro antibody contributes to leucopenia, and cutaneous and neonatal lupus. Objectives: To evaluate the association between serum IL-10 levels and autoantibodies, disease activity and organ involvement in systemic lupus erythematosus (SLE) patients. Patients and methods: We studied 200 SLE patients and 50 controls. We analyzed organ involvement, disease activity, serum IL-10 and interleukin-6 (IL-6) levels, and antinuclear and antiphospholipid antibody profiles. Results: Serum IL-10 and IL-6 levels were higher in SLE patients than in controls (allp< 0.00001). Serum IL-10 levels were positively correlated with IL-6 (p< 0.00001), CRP (p< 0.00001), fibrinogen (p= 0.003), and ESR (p< 0.00001), and negatively correlated with hemoglobin (p= 0.0004) and lymphocytes (p= 0.01). Serum IL-6 levels were positively correlated with CRP (p< 0.00001), fibrinogen (p= 0.001), and ESR (p< 0.00001); and negatively correlated with hemoglobin (p= 0.008) and lymphocytes (p= 0.03). Elevated serum IL-10 levels were associated with an increased risk of anti-SS-A/Ro antibody positivity (p= 0.03). Elevated serum IL-6 levels were associated with an increased risk of heart (p= 0.007) and lung (p= 0.04) involvement. Conclusions: In SLE patients, increased serum IL-10 levels were associated with increased disease activity and risk of anti–SS-A/Ro antibody positivity.