Background: Cytokines have an important immunological role in the pathogenesis of systemic lupus erythematosus (SLE) and they were considered as disease activity biomarkers. This study was conducted to evaluate serum interleukin (IL) -2 and IL-10 levels in relation to disease activity in children and adolescence with SLE. Methods: Sixty lupus patients were studied in comparison to 30 healthy-matched control children. Disease activity was assessed according to SLE Disease Activity Index (SLEDAI). Serum IL-2 and IL-10 were measured by ELISA and their ratio was calculated. Results: Thirty lupus patients had an active disease (SLEDAI ≥ 4) and 30 had low disease activity. Serum IL-2 levels were significantly lower in patients with active disease (148.90±65.88 ng/l) and patients with low disease activity (159.33±68.01 ng/l) than controls (206.40±80.08 ng/l), P<0.01, without significant relation to disease activity. In contrast, serum IL-10 levels were significantly higher in patients with active disease [4064 (1777.5-8462.75) pg/l] and patients with low disease activity (1403 (922.25-2726) pg/l] than controls [7.35 (6.55-8.50) pg/l], (P<0.01) with a significant relation to disease activity (P<0.01). The calculated IL-10/IL-2 ratio was significantly higher in patients with active disease [32.28 (11.44-49.19)] and patients with low disease activity [11.15 (5.25-21.36)] than controls [0.037 (0.031-0.045)] with a significant relation to disease activity (P<0.01). IL-10/IL-2 ratio was more specific and sensitive in evaluating disease activity than IL-10 and IL-2 with test accuracy 89%. Conclusions: IL-10/IL-2 ratio was elevated in lupus patients due to reduced serum IL2 and elevated serum IL-10 levels and it was associated with disease activity