Numerous post-vaccine complications have been reported secondary to the COVID-19 vaccine. Many of these complications are believed to be due to a hyperactive immune system. A 59-year-old woman developed diffuse abdominal pain two days after receiving the mRNA-1273 COVID-19 vaccine (Moderna). A computerized tomography (CT) angiogram of the abdomen and pelvis revealed the presence of numerous vascular irregularities in the celiac axis, bilateral renal arteries, and inferior mesenteric artery consistent with polyarteritis nodosa (PAN), a medium-vessel vasculitis. The patient was managed with intravenous methylprednisolone 500 mg daily for three days and was then placed on oral methotrexate (MTX) 12.5 mg daily for immunosuppressive maintenance treatment. Until now, a limited number of cases of polyarteritis nodosa secondary to the COVID-19 vaccine have been reported. Major mechanisms of post-vaccine autoimmunity are molecular mimicry and autoantibody production. Although rare adverse events from COVID-19 vaccination are possible, there remains an immense benefit to vaccination in preventing COVID-19-related morbidity and mortality.