Previous studies have shown that pregnant women with systemic lupus erythematosus (SLE) tend to have a higher risk of adverse pregnancy outcomes, but the potential causal role remained unclear. In this study, we aimed to investigate the causal relationship between SLE and some common pregnancy complications and outcomes using two-sample Mendelian randomization (MR).The genetic tools were derived from genome-wide association studies of SLE and pregnancy complications and outcomes. MR analysis was performed using inverse variance weighting as primary method. Sensitivity analyses were performed to evaluate the robustness of the results. A retrospective analysis was conducted on 200 pregnant women with SLE and a control group of pregnant women delivering at Tongji Hospital.In the results, we found that genetic susceptibility to SLE was associated with a higher risk of gestational diabetes mellitus (OR = 1.028, 95% CI: 1.006-1.050), premature delivery (OR = 1.039, 95% CI: 1.013-1.066), polyhydramnios (OR = 1.075, 95% CI: 1.004-1.151) and premature rupture of membranes (OR = 1.030, 95% CI: 1.001-1.060). Some of the retrospective analysis results align with the findings from the MR analysis, indicating that pregnant women with SLE have a higher risk of developing gestational diabetes mellitus and preterm birth. Additionally, although MR analysis did not reveal a causal relationship between SLE and preeclampsia/eclampsia, retrospective analysis discovered that SLE pregnant women are more susceptible to developing preeclampsia/eclampsia (OR = 2.935, 95% CI: 1.118-7.620).Our study findings suggest a potential causal relationship between SLE and increased risks of gestational diabetes and preterm delivery. Clinical data indicate that pregnant women with SLE are more prone to developing preeclampsia/eclampsia. Clinicians need to be vigilant about the occurrence of these conditions when managing pregnant women with SLE.© 2024 Zhu et al.