Cytomegalovirus (CMV) is common in immunocompromised patients and in patients taking immunosuppressants. Infection with CMV can manifest as an exacerbation of mucosal inflammation. Whether CMV is an active pathogen or “an innocent bystander” in the exacerbation of ulcerative colitis remains controversial. Though rare, still CMV colitis must be considered in the differential diagnosis in immunocompetent patients in whom there is no relief in diarrhea or abdominal pain with antibiotics. If not diagnosed promptly there can be a bowel perforation leading to poor prognosis. In unexplained diarrhea cases, endoscopic biopsy and measurement of CMV immunoglobulin (Ig) M antibody level are warranted. We present a case study of a 51-year-old male with complaints of loose motions, abdominal pain, and generalized weakness. He was not on immunomodulators like steroids and was managed as a routine case of infective bacterial diarrhea. Initially, the patient's symptoms resolved but later because of drowsiness and abdominal distension, he had to be shifted to the intensive care unit (ICU). His endoscopic biopsy was done which was suggestive of CMV colitis. He was prescribed ganciclovir—intravenous (IV) and considerable improvement was seen. The patient was discharged in a hemodynamically stable condition. From this case one can conclude that CMV colitis in immunocompetent hosts is rare but strong clinical vigilance can help in preventing further worsening of symptoms.