Pregnancy is associated with extraordinary plasticity in the maternal brain. Studies in humans and other mammals suggest extensive structural and functional remodeling of the female brain during and after pregnancy. However, we understand remarkably little about the molecular underpinnings of this natural phenomenon. To gain insight into pregnancy-associated hippocampal plasticity, we performed single nucleus RNA-seq and single nucleus ATAC-seq from the mouse hippocampus before, during, and after pregnancy. We identified cell-typespecific transcriptional and epigenetic signatures associated with pregnancy and post-partum adaptation. In addition, we analyzed receptor-ligand interactions and transcription factor motifs that inform hippocampal cell type identity and provide evidence of pregnancy-associated adaption. In total, this data provides a unique resource of coupled transcriptional and epigenetic data across a dynamic time period in the mouse hippocampus and suggests opportunities for functional interrogation of hormone-mediated plasticity.