Osmotic demyelination syndrome (ODS) is a rare but serious condition that is hypothesized to be a result of rapid correction of hyponatremia, with a catastrophic prognosis. The foci of demyelination may occur in either the pontine area or within the white matter of the cerebral hemispheres, which denotes a specific clinical presentation. We present the case of a post-COVID-19 patient who was diagnosed with ODS with typical clinical and radiological characteristics of both forms: central pontine myelinolysis and extrapontine myelinolysis. The clinical assessment of ODS encompasses a variety of differential diagnoses, including stroke, neuroinfection, neoplasia, and other demyelinating diseases. A specific characteristic of ODS is the delayed clinical manifestation after the hyponatremic state. Furthermore, it is noteworthy that there might be discrepancies between the clinical manifestations and the neuroimaging findings. The association between COVID-19 and ODS is unclear at the moment, although it can possibly be explained by the viral infection through multiple mechanisms such as renal dysfunction, diarrhea, or vomiting. ODS should be considered in cases of hyponatremia and neurological deterioration during the course of COVID-19 infection. Despite the fact that early detection and treatment of this syndrome can reduce the risk of short-term mortality and long-term disability, they do not guarantee complete recovery.