INTRODUCTION: We examined the effect of infection with each of the most common SARS-CoV-2 variants during pregnancy on the development of preeclampsia. METHODS: This was an IRB-approved retrospective cohort study of patients at our academic hospital from January 1, 2019 to December 30, 2022. Primary outcomes were rates of preeclampsia among those with and without SARS-CoV-2 infection during pregnancy, specifically comparing the periods when the most common SARS-CoV-2 variants (Alpha, March 15 to June 21, 2021; Delta, June 21 to December 20, 2021; and Omicron, December 20, 2021 to December 30, 2022) were the most frequently diagnosed variant. The secondary outcome was characteristics of placental pathology. RESULTS: Six thousand three hundred fifty-eight charts were reviewed, 6,182 met inclusion criteria, and 657 tested positive for SARS-CoV-2 during pregnancy. There were 109 cases prior to the identification of the Alpha variant, 14 Alpha, 72 Delta, and 462 Omicron cases. All variants were associated with an increase in preeclampsia (P=.006). In adjusted models, the pre-Alpha infection was associated with a 2.12-fold increase in preeclampsia (P=.003), and Omicron infection was associated with 2.11-fold increase in severe preeclampsia (P=.01). Infections with Omicron and Delta were associated with an increase in placental intervillous thrombi (30.8% and 16.5% versus 12.5% in no infection; P=.014). Intervillous thrombi was seen 3.25 times more after Delta infection in adjusted models (P=.001). CONCLUSION: Adjusted models showed an increase in preeclampsia rates with pre-Alpha and severe preeclampsia with Omicron variant infections. Delta infection was associated with an increase in thrombotic vasculopathy within the placenta. These findings suggest differing levels of concern by viral variant and may help direct counseling should additional variants emerge.