Identification of susceptibility genes in systemic lupus erythematosus (SLE) has recently become a topic of interest. The IL-10 promoter contains three single base-pair substitutions at −627C > A, −854C > T and −1117G > A. These single base-pair substitutions produce three different haplotypes, GCC, ACC and ATA, which affect IL-10 expression. We examined the distribution of −627C > A, −854C > T and −1117G > A IL-10 promoter polymorphisms in patients with SLE (n = 103, women only) and matched controls (n = 300). Despite the higher prevalence of the GCC/GCC, GCC/ATA and ATA/ATA genotypes in SLE patients than in controls, we observed that only GCC/GCC genotype frequency distribution was significant between these groups. We observed that women with the GCC/GCC genotype displayed an approximately twofold increased risk of SLE OR = 2.245 (95% CI = 1.354–3.721, P = 0.0022). We did not find any associations between various genotypes of IL-10 promoter haplotypes and clinical manifestations or autoantibody production in patients with SLE. Our observations indicate that the GCC/GCC promoter genotype may contribute to SLE incidence in Polish patients.