Cytomegalovirus (CMV) is a human herpes-type virus with variable clinical manifestations. Infections in immunocompetent patients are usually asymptomatic or mild, and severe infections are generally seen in immunosuppressed individuals. CMV colitis is not uncommon in patients with ulcerative colitis (UC) and is mostly associated with the use of steroids, immunomodulators like azathioprine, and biologics like infliximab, which have systemic immunosuppressive effects. Vedolizumab is an anti-integrin antibody that is gut-selective without any systemic effects. We report an unusual presentation of a female patient with UC who had concomitant CMV colitis and erythema nodosum, who was on vedolizumab, and not on any steroids or other immunosuppressants. She responded well to anti-viral treatment and steroids.