Purpose <p>To report a challenging case of cytomegalovirus retinitis (CMVR) in a Human immunodeficiency virus (HIV) negative patient with diabetes mellitus.</p> Methods <p>This is a case report about a patient who was diagnosed with diabetes mellitus type 2 and treated for chronic lymphoproliferative disease (CLD). The patient developed clinical signs of cytomegalovirus retinitis (CMVR). The patient underwent a thorough diagnostic workup and complex treatment. We present the outcomes of treatment in this challenging case.</p> Results <p>67-year-old man initially diagnosed with both eyes mild non-proliferative diabetic retinopathy (NPDR) presented with blurred vision in the right eye. The patient presented with hypertensive anterior CMV-related anterior uveitis. The baseline visual acuities were 6/9 in both eyes with elevated IOP in the right eye (31mmHg). Dilated fundus examination revealed right eye peripheral retinitis accompanied by haemorrhages. The anterior tap confirmed the presence of CMV, and antiviral treatment has been commenced. Despite the treatment with antiviral agents, the patient developed a right eye occlusive disease along with macular edema. The patient underwent right eye pan-retinal photocoagulation (PRP) laser therapy to address occlusive and non-perfused areas in conjunction with intravitreal anti-VEGF agents. Over time, the patient achieved disease quiescence.</p> Conclusion <p>CMV retinitis in immunocompromised, HIV-negative patients with diabetes presents significant diagnostic and therapeutic challenges. Importantly, the potential development of immune recovery uveitis (IRU) – like picture should be carefully considered during the recovery phase, as it may contribute to further vision loss if not promptly recognized and managed. This case highlights the importance of individualized, multidisciplinary care and close monitoring during both the active and post-treatment phases.</p>