Background Oral infection of mice with P. gingivalis induces periodontal inflammation and attachment loss. The aim of the present study was to investigate whether infection of mice with P. gingivalis, exacerbates the clinical course of experimental autoimmune encephalomyelitis (EAE)—a mouse model of multiple sclerosis (MS). Methods Induction of EAE was carried out by immunization of C57BL/6 mice with myelin oligodentrocyte glycoprotein (MOG35‐55). P. gingivalis infection was induced via subcutaneous chambers model and the oral gavage. The severity of EAE was measured using a clinical severity score. Ex‐vivo reactivation of lymphocytes with the encephalitogenic peptide MOG35‐55 was also tested. Results Subcutaneous as well as oral infection with live P. gingivalis led to significant aggravation of the severity of EAE. Lymph node cells harvested from mice with EAE following P. gingivalis infection showed augmented lymphocyte proliferation towards the encephlatigenic MOG moiety compared to mice with EAE only. Conclusions The present results indicate that oral infection with P. gingivalis augmented the severity of EAE. This may stem from the systemic pro‐inflammatory response triggered by P. gingivalis infection or via antigen mimicking. The present study provides evidence that periodontal infection may play a role as modifier in CNS inflammatory disorders, such as MS.