Interleukin (IL)-10 expression is regulated by its promoter and correlated with the activity of adult-onset lupus (systemic lupus erythematosus (SLE)). As the pathogenesis of adult-onset SLE may differ from SLE with the age at onset <18 years old (juvenile SLE or JSLE), we evaluated polymorphisms at positions -1082A/G, -819T/C and -592A/C of the IL-10 promoter and serum IL-10 levels in 71 patients with JSLE. Disease activity was determined by the SLE disease activity index (SLEDAI). Active SLE was defined by SLEDAI ≥ 6 and inactive SLE was defined by SLEDAI equal to zero. The mean age was 14.5 ± 2.8 years. Nephritis occurred in 57 patients. In JSLE patients, -592 CC and -819 CC were identified with a higher frequency than in controls with the odds ratio (OR) of 2.75 (95% confidence interval (CI) 1.11-6.81, p = 0.04). GCC increased the susceptibility to nephritis in patients with JSLE (OR 2.16, 95% CI 1.07-4.35, p = 0.03). Serum IL-10 levels were significantly higher in 20 JSLE patients with active disease than in 27 patients with inactive disease and in 15 healthy children (p < 0.001). In conclusion, IL-10 expression was upregulated in active JSLE. The -819 CC and -592 CC genotypes increased the susceptibility to JSLE and GCC increased the susceptibility to nephritis.