Objective: Single nucleotide polymorphisms (SNPs) in the displacement-loop (D-loop) area of mitochondrial deoxyribonucleic acid (mtDNA) were found to be associated with an increased risk of systemic lupus erythematosus (SLE) in our previous research. This study mainly focused on the correlation of SLE risk-associated SNPs in the D-loops and the oxidative stress status. Methods: In total, 81 female Chinese patients diagnosed with SLE and 102 age-matched female controls were involved in this research from May 2017 to October 2017. The oxidative stress status was confirmed by measuring the reactive oxygen species (ROS) levels in the blood of SLE patients and controls. Student's t test was used to compare ROS levels between SLE patients and controls. Wilcoxon rank-sum test was used to analyze the correlation among SLE risk-associated SNPs, the clinical features and ROS levels. Results: The levels of ROS in SLE patients were remarkably higher than those in controls (655.025 +/- 49.748 vs. 533.284 +/- 30.033, P=0.030, 95% CI: 11.886, 231.595). In addition, the active SLE patients exhibited higher ROS generation compared with that of controls. Furthermore, the SLE susceptible SNP of 195T was linked with higher ROS generation (T: 41.823, C: 8.5, P=0.048). Conclusion: In summary, the SLE risk associated SNPs in the D-loop may initiate SLE by boosting oxidative stress levels.