Most cases of cytomegalovirus (CMV) colitis in patients with inflammatory bowel disease (IBD) occur in those treated with immunosuppressants and/or corticosteroids. We herein present the case of a 57-year-old man with toxic megacolon associated with CMV colitis in corticosteroid-naïve ulcerative colitis (UC). To date, there have been only eight previous case reports of CMV colitis in steroid-naïve UC. We discuss the need to consider CMV colitis when making a differential diagnosis of patients with refractory UC who are not receiving corticosteroid treatment.