Background: Multiple sclerosis (MS) with onset in the setting of acute SARS-CoV-2 virus infection has been reported, and reactivation of MS following non-mRNA COVID-19 vaccination has been noted, but there have only been three reports of newly diagnosed MS following exposure to mRNA COVID-19 vaccine. The association cannot be determined to be causal, as latent central nervous system demyelinating disease may unmask itself in the setting of an infection or a systemic inflammatory response. We report a series of 5 cases of newly diagnosed MS following recent exposure to mRNA COVID-19 vaccines. Latency from vaccination to initial presentation varied. Neurological manifestations and clinical course appeared to be typical for MS including response to high dose steroids in 4 cases and additional need for plasmapheresis in one case. Conclusion: Acute neurological deficits in the setting of recent mRNA COVID-19 vaccine administration may represent new onset multiple sclerosis.