Background: FOXP3, an important transcription factor of regulatory T cells has shown a contribution to the development of various autoimmune diseases. Objectives: To investigate the influence of FOXP3 polymorphisms (rs3761548 and rs2294021) on systemic lupus erythematosus (SLE) susceptibility and patients' characteristics. Methods: Genotyping was performed on 265 patients with SLE and 404 healthy controls using PCR-RFLP. Patients' demographic, laboratory, and clinical information were all documented. The relationship between the SNPs and patients' characteristics was statistically analyzed. Results: The frequency of C/- genotype in male patients was significantly higher than in the healthy male controls, whereas the frequency of A/- genotype was lower (OR=0.53; 95% CI=0.28-1.00, p=.05). Analysis of the correlation between these SNPs and the patients' characteristics showed a longer disease duration in the rs3761548 C/- carriers and a correlation with arthralgia in both SNPs. In the females, there was a significant association between CC haplotype and disease susceptibility (OR=0.6, CI=0.38-0.94, p=.027). A significant association of both SNPs with the history of abortion was also detected. The frequencies of the rs3761548 AA (p=.006) and the rs2294021 CC genotypes (p=.038) and AC/AC combination (p=.033) were higher in women who had an abortion. We found a correlation between the rs3761548 AC genotype and the decreased C4 level and cardiovascular involvement, and the rs2294021 CC genotype with ESR, neurological involvement, and photosensitivity. Conclusions: FOXP3 rs3761548 C/- genotype association with disease susceptibility in male patients, an association of both SNPs with the abortion risk in female patients, and the correlation between these SNPs and several clinical features of the patients suggest their association with the disease development and pathology.