AbstractThere is a growing body of evidence that innate immunity also plays an important role in the progression of hepatitis B virus (HBV) infection. However, there is less study on systematically elucidating the characteristics of innate immunity in HBV‐infected pregnant women. We compared the features of peripheral blood mononuclear cells in three healthy pregnant women and three HBV‐infected pregnant women by single‐cell RNA sequencing. 10 DEGs were detected between groups and monocytes were the main expression source of most of the DEGs, which involved in the inflammatory response, apoptosis and immune regulation. Meanwhile, qPCR and ELISA were performed to verify above genes. Monocytes displayed immune response defect, reflecting poor ability of response to IFN. In addition, eight clusters were identified in monocytes. We identified molecular drivers in monocytes subpopulations.TNFSF10+monocytes,MT1G+monocytes andTUBB1+monocytes were featured with different gene expression pattern and biological function.TNFSF10+monocytes andMT1G+monocytes were characterized by high levels of inflammation response.TNFSF10+monocytes,MT1G+monocytes andTUBB1+monocytes showed decreased response to IFN. Our results dissects alterations in monocytes related to the immune response of HBV‐infected pregnant women and provides a rich resource for fully understanding immunopathogenesis and developing effective preventing HBV intrauterine infection strategies.