Viral infections, such as cytomegalovirus (CMV) infection, may affect the clinical course of ulcerative colitis (UC). CMV can cause chronic inflammation of the intestinal mucosa. In inflammatory bowel disease, chronic inflammation caused by CMV can deter the regeneration of the mucosa of the colon. However, the relationship between CMV and inflammatory bowel disease still needs to be clarified, especially in immunocompetent patients, such as younger patients not treated with immunosuppressants. Herein, we describe our experience with a middle-aged immunocompetent female patient diagnosed with fulminant UC positive for myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA). Her initial response to high-dose prednisolone was favorable; however, remission was not achieved. Immunohistochemical staining revealed the presence of CMV. Subsequently, the patient was successfully treated with prednisolone, adalimumab, and azathioprine, along with the anti-CMV treatment comprising valganciclovir. This case shows that the presence of CMV in the mucosa and blood may make patients with UC refractory to immunosuppression; furthermore, the positivity of MPO-ANCA in patients with UC can necessitate the administration of high-dose immunosuppressants to taper the dose of prednisolone.