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Transient splenial lesion of the corpus callosum can be observed in various diseases such as cancer, drug use, metabolic disorders, and cerebrovascular disorders, as well as in patients with infectious diseases. During the coronavirus disease 2019 (COVID-19) pandemic, there were increasing reports of these lesions being detected on brain imaging tests performed in patients with neurological symptoms. On brain magnetic resonance imaging, findings suggestive of cytotoxic edema are observed in the splenium; these are known to disappear with improvement of clinical symptoms. Cytokinopathy caused by infection increases the permeability of the blood–brain barrier and activates the glial cells of the brain to induce cytotoxic edema. Most patients have a good prognosis. The causes, mechanism, diagnosis, treatment and prognosis of transient splenial lesions of the corpus callosum will be summarized in this review.