Olfactory impairment occasionally occur in autoimmune central nervous system (CNS) inflammation, including multiple sclerosis. The aim of this study was to evaluate whether olfactory impairment occurs in experimental autoimmune encephalomyelitis (EAE) as an animal model of multiple sclerosis. EAE was induced by immunization of myelin oligodendrocyte glycoprotein (MOG) peptides in C57BL/6J mice. Bioinformatic and immunohistochemical analyses were done in the olfactory bulbs and olfactory mucosa with EAE. Behavioral tests revealed that the searching time for a bait was significantly delayed in EAE mice. Neuroinflammatory lesions, characterized by microgliosis and astrogliosis, were identified in the olfactory bulbs with EAE. Inflammatory cells were also found along the olfactory nerves and in the submucosa of olfactory mucosa. Western blot analysis of olfactory marker protein (OMP) showed that OMP was significantly downregulated in the olfactory mucosa with EAE. Differentially expressed genes (cut-offs, fold change > 2 and adjusted p < 0.05) and their related pathways in olfactory bulbs were subjected to gene ontology (GO) pathway analysis and gene set enrichment analysis (GSEA). Twelve hub genes were found, three of which (Ctss, Itgb2, and Tlr2) were validated by qPCR to be related to GO pathways such as immune response and regulation of immune response. GSEA showed that neuron-related genes including Atp6v1g2, Egr1, and Gap43 and their pathways were significantly downregulated. Collectively, the present data imply that neuroinflammation in the olfactory pathway induces olfactory impairment in EAE, which was further evidenced by bioinformatic analysis. * This research was supported by the National Research Foundation of Korea (Grant number: NRF- 2019R1A2C1087753).