Acute disseminated encephalomyelitis (ADEM) is a relatively rare, post-inflammatory, immune-mediated demyelinating central nervous system disease that is predominantly reported in pediatric populations. Following the emergence of severe acute respiratory syndrome coronavirus 2, cases of ADEM are being reported following infection with this virus. Our case report describes a male patient in his early 40s who developed severe coronavirus disease 2019 (COVID-19) that rapidly progressed to a critical disease requiring invasive mechanical ventilation and high positive end-expiratory pressure, which was complicated by extensive neurological involvement and quadriplegia. MRI of the brain showed characteristic demyelinating lesions, suggestive of ADEM. As other entities were ruled out, our patient was treated using pulse steroids and intravenous immunoglobulins. The patient showed a good response to treatment and had an overall good prognosis, despite the severity of his condition. ADEM following COVID-19 is a rare entity worldwide.