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Retinitis is the most frequent manifestation of Cytomegalovirus (CMV) disease in patients with HIV infection. The virus reaches the retina by hematogenous spread, therefore patients with serum CMV load are at increased risk of developing CMV retinitis. The evolution of retinitis without specific treatment causes irreversible visual loss. Proper treatment is essential for controlling the disease progression, prevention of relapses, and contralateral eye involvement. This report describes a 56-year-old white male who started a progressive decrease in visual acuity (VA) of the right eye, without pain or inflammatory signs. Initial fundoscopy identified a dispersed preretinal hemorrhage and yellowish exudates. For the hypothesis of CMV retinitis, serology for HIV was requested and the subsequent result was positive. Other opportunistic infections, as well as manifestations of CMV infection in other organs, were ruled out. The patient was discharged on valganciclovir and highly active antiretroviral therapy (HAART) with progressive improvement in retinal changes, but without full recovery from VA due to chronic vitritis and tractional retinal detachment. Slow recovery of lymphocyte populations and sustained decrease in viral load were observed. CMV retinitis as an initial and sole manifestation of HIV infection is rare and requires screening. The importance of this case lies in its rarity, since CMV retinitis was the only manifestation of CMV infection and the only opportunistic infection in this patient. Early diagnosis and initiation of targeted therapy decrease the morbidity associated with this infection.