Type I interferons are most commonly associated with their essential role in the innate immune response. However, the actions of the type I interferon receptor are not limited to the scenario of infection. Previous work from our group revealed that type I interferon receptor signaling, specifically in a subtype of glia cells (astrocytes), critically modulates hippocampal synaptic plasticity and cognitive function in adult mice under physiological conditions. Since cytokines such as type I interferons are implicated in modulation of neurogenesis and brain development, in this work we started to unravel the role of the type I interferon receptor (IFNAR) signaling in brain development. For this study, three weeks old IFNAR KO mice and animals with a cell type-specific IFNAR KO in astrocytes (GFAPCreIFfl) or neurons (SynCreIFfl) were used. Golgi-Cox staining revealed a sex-specific reduction in spine density in female IFNAR KO mice in the hippocampal CA1 and DG-inferior which was not present in males or SynCreIFfl. Furthermore, immunostainings in female IFNAR KO mice showed a significant increase in the density of astrocytes in the respective hippocampal sub-regions. Single cell analysis of microglia and astrocytes provided evidence for altered synaptic pruning mediated by microglia and astrocytes in female IFNAR KO animals in specific hippocampal sub-regions. In summary, this work highlights the important physiological role of the type I interferon receptor in brain development and opens up new insights in sex-specific as well as cell-type specific effects.