Introduction: Ulcerative colitis is a chronic disease characterized by inflammation of the colonic mucosa that results in symptoms of diarrhea, passing blood per rectum, and in severe cases, abdominal pain, colonic distension, and other signs of toxicity including fever. However, other etiologies have similar symptoms resulting in increasing difficult diagnosing flares versus infections, especially given the use of immunosuppressives. We present a case of a patient with ulcerative colitis who experienced multiple infections as a result of immunosuppression. Case: 67 year-old male presented with severe bloody diarrhea. Colonoscopy revealed colonic mucosa ulcerations, loss of vascularity, and bleeding compatible with inflammatory bowel disease and biopsies revealed chronic colitis. After excluding infectious causes a diagnosis of pancolonic ulcerative colitis was made. Over a course of a year, he was treated with mesalamine and several courses of prednisone (intravenous and oral). Two months into therapy he had worsening in his symptoms. His stool was positive for Clostridium difficile and he was treated with metronidazole for two weeks. Repeat testing for clostridium was negative. Repeat colonic mucosa biopsies were positive for inclusion bodies and positive staining for cytomegalovirus (CMV). He was treated with gancyclovir for three months. Unfortunately, his symptoms would relapse every time steroids were tapered down. Once gancyclovir was stopped, he was admitted with another episode of worsening of his diarrhea and repeat colonic biopsies showed CMV again. At this time he developed shortness-of-breath and CT scan of the chest revealed pulmonary embolism for which he had to be anticoagulated. He was started on infliximab with no immediate relief. The patient elected at that point to proceed with surgical management and he underwent a laparoscopic total proctocolectomy with terminal ileostomy. Discussion: Ulcerative colitis clinical course can be severe and complicated in some patients. Health-care providers should be aware of other etiologies that mimic ulcerative colitis flare-like symptoms, especially in these patients who have received immunosuppression.