Since its first systematic description, multiple sclerosis has been associated with cognitive and behavioral symptoms. Among psychiatric syndromes, mood disorders are highly common. Herein we report a case of a manic episode following a multiple sclerosis relapse in a young male subject without past history of psychiatric illness. The patient’s psychiatric symptoms influenced negatively his adhesion to treatment, possibly impacting his prognosis. Multiple sclerosis may be considered in the differential diagnosis of young adults presenting major psychiatric syndromes, including mania.