Objective <p>To describe causes, clinical manifestations, imaging features and prognosis of reversible splenial lesion syndrome (RESLES) in children.</p> Methods <p>A total of 36 patients with RESLES hospitalized in Children’s Hospital of Chongqing Medical University between January 1, 2017 and Mar 31, 2024 were included. The clinical features including the causes, clinical manifestations and prognosis were statistically analyzed.</p> Results <p>The patients’ ages ranged from 16 to 170 months with a median age of 49 months. Of the 36 patients, 24 patients were RESLES type-1 (the lesions were limited to SCC) and 12 patients were RESLES type-2(the lesions spread to other parts of the corpus callosum, extensive brain white matter, or both). The participating causes included infection, chemotherapy, immunoglobulin A vasculitis, autoimmune glial fibrillary acidic protein astrocytopathy, hypertension and hypoparathyroidism. The common neurological symptoms were seizures(<i>n</i> = 27), headache(<i>n</i> = 10), dizziness(<i>n</i> = 6), altered consciousness(<i>n</i> = 8), and psychologico-behavioral abnormalities(<i>n</i> = 14). Most patients had a good prognosis except 1 patient remained in a state of minimal consciousness during the follow-up.</p> Conclusion <p>This research demonstrates some possible causes of RESLES. Patients with RESLES present with a variety of nonspecific symptoms and most of them had a good prognosis.</p> Significance <p>These findings are groundbreaking to a deeper understanding of RESLES.</p>