As the novel coronavirus, SARS-CoV-2, has enveloped the world in a pandemic, it has become clear that the symptoms extend far beyond the respiratory system and have particularly caused a wide range of neurologic CNS complications, including diffuse leukoencephalopathy. Here, we describe a case of a 59-year-old male with severe COVID-19 infection who developed severe encephalopathy, which persisted well after his acute infection had subsided and had begun to improve from his respiratory dysfunction. He was found to have diffuse leukoencephalopathy with concomitant diffusion restriction on MR imaging. This case represents a delayed onset of leukoencephalopathy secondary to hypoxia in a small but growing cohort of COVID-related leukoencephalopathy due to similarities in imaging features and lack of superior alternate diagnosis. Patient's clinical improvement suggests reversibility with likely pathology being demyelination rather than infarction.