Cytomegalovirus (CMV) can be a reason for severe disease in immunocompromised patients, either via the reactivation of latent CMV infection or via the acquisition of primary CMV infection. Clinical syndromes that may be observed are retinitis, colitis, esophagitis, encephalitis, pneumonitis, hepatitis, uveitis, and graft rejection following transplantation. The simultaneous occurrence of CMV colitis and retinitis as the initial presentation of human immunodeficiency virus (HIV) infection is extremely rare. We present a case of a 42year-old male, known to have type 2 diabetes, bronchial asthma, and allergic rhinitis, who presented to the emergency department (ED) with two weeks history of abdominal pain and watery diarrhea four to five times per day sometimes accompanied by small amounts of blood. He also had an on-and-off subjective fever for the last two months prior to presentation, loss of appetite, and weight loss of 13 kg over the last six months. Additionally, he had a history of travel outside Saudi Arabia and unprotected sex. HIV-1 serology (combination antigen/antibody immunoassay) was requested, which came out positive, with a viral load of 323141 copies/mL and decreased CD4+ T lymphocytes (0 cel/μL). CMV polymerase chain reaction (PCR) quantitative was detected and the CMV viral load was 694963 IU/mL. Given the patient's bloody diarrhea with positive CMV and HIV, the gastroenterology team was consulted and they decided to proceed with a colonoscopy and biopsy. The patient was diagnosed with CMV colitis based on the biopsy results. The patient also was found to have CMV retinitis based on ophthalmologic assessment. Multidisciplinary teams, including infectious diseases, gastroenterology, ophthalmology, and pathology, should cooperate to facilitate an accurate and fast diagnosis. Further complications can be prevented by early diagnosis and treatment.