Background:Evidence suggests that DNA damage is implicated in the development of Systemic Lupus Erythematosus (SLE). Objective:Investigate the possible association of polymorphisms in the DNA repair genes XRCC1 and XRCC3 with SLE and its clinical and laboratory features. Methods:This is a case-control study comparing the polymorphisms in the DNA repair genes XRCC1 and XRCC3 in SLE patients and control individuals. Genotyping for DNA repair genes was performed by polymerase chain reaction-restriction fragment length polymorphism in 76 patients and 82 healthy control individuals. Results:Our data indicated that the genotype frequencies in patients with the XRCC1 Arg399Gln and XRCC3 Thr241Met polymorphisms were similar to those observed in the control group (p > 0.05). However, the frequencies of the 399Gln allele (p = 0.023, OR = 0.58, 95% CI = 0.36-0.93) and 241Met allele (p = 0.0039, OR = 0.59, 95% CI = 0.36-0.98) were significantly lower in the patients than those in the control subjects. Conclusion:We demonstrated that 399Gln and 241Met alleles may play a protective role in SLE susceptibility.