Background: Cytomegalovirus (CMV) infections are common, especially in immunocompromised patients. These infections are usually asymptomatic but can become symptomatic in immunocompromised individuals, with colitis being the second most common presentation of end-organ disease. CMV colitis can mimic Inflammatory Bowel Disease (IBD) or cause an IBD flare, thus making the diagnosis challenging. Case Report: We describe the case of a 69-year-old male known to have Chronic Lymphocytic Leukemia (CLL) maintained in remission on venetoclax, a BCL-2 inhibitor. The patient was recently started on mesalamine and steroids after a Crohn’s Disease (CD) diagnosis three weeks before presentation. The patient presented with bloody diarrhea and abdominal pain. His workup included a colonoscopy that showed skip lesions (diffuse ulcerated lesions separated by areas of normal mucosa), a characteristic of CD. Ileal and colonic biopsies were sent for Polymerase Chain Reaction (PCR) of CMV and turned out positive. Therefore, the patient was diagnosed with CD with superimposed CMV colitis. We started the patient on ganciclovir. Three months later, a repeat colonoscopy revealed complete resolution of mucosal ulcerations, practically changing the diagnosis to an isolated CMV colitis mimicking CD. Conclusion: An isolated CMV colitis can mimic CD, and physicians must consider this entity in their differential diagnosis. This case is additionally remarkable because CLL and the use of a BCL-2 inhibitor usually have a protective role against CMV disease, but this was not the case for our patient.