The olfactory epithelium (OE) is a site of massive adult neurogenesis where olfactory sensory neurons (OSNs) are continuously turned over. Tissue macrophages have been implicated in phagocytosis of degenerating cells but the molecular mechanisms that allow for their recruitment while maintaining a neurogenic microenvironment are poorly understood. This study reports that the neuroprotective chemokine CX3CL1 is expressed by OSNs and olfactory ensheathing cells. Monocyte-derived cells in the OE depend on CX3CL1-signalling for intraepithelial migration and apical dendrite expression. These observations are first to demonstrate phenotypic differences in appearance and distribution of monocyte-derived cells in nervous tissue due to CX3CR1 deficiency.