BackgroundInfants receive their first bacteria from their birthing parent. This newly acquired microbiome plays a pivotal role in developing a robust immune system, the cornerstone of long-term health.ResultsWe demonstrated that the gut, vaginal, and oral microbial diversity of pregnant women with SARS-CoV-2 infection is reduced, and women with early infections exhibit a different vaginal microbiota composition at the time of delivery compared to their healthy control counterparts. Accordingly, a low relative abundance of twoStreptococcussequence variants (SV) was predictive of infants born to pregnant women with SARS-CoV-2 infection.ConclusionsOur data suggest that SARS-CoV-2 infections during pregnancy, particularly early infections, are associated with lasting changes in the microbiome of pregnant women, compromising the initial microbial seed of their infant. Our results highlight the importance of further exploring the impact of SARS-CoV-2 on the infant’s microbiome-dependent immune programming.Video AbstractSupplementary InformationThe online version contains supplementary material available at 10.1186/s40168-023-01577-z.