The use of steroids and other immune modulatory therapies in the treatment of severe COVID-19 pneumonia predisposes patients to the reemergence of opportunistic infections. Cytomegalovirus (CMV) reactivation can be one of them. A 55-year-old gentleman with severe COVID-19 pneumonia and hypoxic respiratory failure who was ventilated and received steroids but no other immunomodulatory drugs; had altered sensorium and multiple episodes of seizures in the later course of his illness. Brain MRI showed leptomeningeal enhancement and encephalopathy changes, electroencephalography (EEG) was suggestive of diffuse encephalopathy and his cerebrospinal fluid (CSF) analysis revealed high Cytomegalovirus PCR DNA titers (103,614). The patient made a complete recovery after treatment with Ganciclovir. Altered sensorium in cases of COVID-19 can be multifactorial. High index of suspicion for reactivation of dormant infections is warranted. CMV meningoencephalitis is one of the differential diagnoses. We believe this is the first case reported of CMV meningoencephalitis in the setting of severe COVID-19 infection.