Background Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is an autoimmune disorder which often presents with neuropsychiatric symptoms. A large proportion of cases are associated with an identifiable tumor, most commonly ovarian teratoma. However, recent literature has also described an overlap of anti-NMDAR encephalitis and demyelinating syndromes. Cases have been reported of anti-NMDAR encephalitis in patients with ADEM, optic neuritis, myelitis and multiple sclerosis. This link is considered rare, however has important clinical implications as treatments and prognosis may differ. Case presentation A 33-year-old female with a history of multiple sclerosis presented with new-onset neuropsychiatric symptoms. After substance-induced psychosis was ruled out, she was admitted to the medical ward for work up of psychosis secondary to multiple sclerosis. However, the consultation-liaison psychiatry service noted atypical symptoms which were concerning for autoimmune encephalitis. Admission to a psychiatric inpatient ward was deferred. Anti-NMDAR encephalitis was diagnosed with CSF analysis demonstrating lymphocytic pleocytosis and anti-NMDAR antibodies. In addition to first-line treatment of encephalitis with steroids, second-line immunotherapies were also implemented given the patient’s underlining demyelinating syndrome. The patient’s neurologic and psychiatric symptoms began to improve. Conclusions There is literature to demonstrate a possible connection between anti-NMDAR encephalitis and demyelinating syndromes. As such, autoimmune encephalitis should be considered in patients with multiple sclerosis presenting with atypical symptoms. Determining the correct diagnosis is crucial to inform the appropriate treatment protocol, and to improve prognosis.