As the rate of autoimmune conditions and cancers is increasing in the United States, a larger number of patients are being managed with immunosuppressive medications. Diarrhea is a common problem in immunocompromised patients. A feared complication of immunosuppression is infection with opportunistic pathogens. Cytomegalovirus is an opportunistic infection that can cause infection in a variety of different organ systems, including affecting the gastrointestinal system. Severe infection is most commonly seen as a complication of acquired immunodeficiency syndrome (AIDS), organ transplant, hematological malignancy, or cancer therapy. This case report describes a case of cytomegalovirus colitis in an immunosuppressed patient following mycophenolate mofetil (CellCept) therapy.