Background: Mild encephalitis/encephalopathy with a reversible isolated splenial lesion (MERS) is a rare and complex clinico-radiological condition that aggregates various diseases. From a geographical point of view, most cases have been reported in Asia, especially in Japan. However, a very limited number of studies have properly evaluated Chinese patients diagnosed with MERS. Methods: Putative encephalitis/encephalopathy patients affected by a reversible isolated SCC lesion, as detected by magnetic resonance imaging (MRI), were retrospectively evaluated. Specifically, we reviewed extensive patient data, including prodromal and neurologic symptoms, neurologic examinations, MRI and electroencephalography (EEG) findings, laboratory results, treatments, and prognosis. Results: Six clinically mild encephalitis/encephalopathy patients, affected by a reversible isolated SCC lesion, were identified in a cohort of 22 patients. Six patients presented fever symptoms before the onset of neurological manifestations. Initial MRI data exhibited isolated SCC lesions with isointense or slightly hypointense on T1WI, hyperintense on T2WI, Flair, and DWI, as well as decreased ADC values, without contrast enhancement. EEG data indicated abnormalities (3/4), as well as elevated serum inflammatory markers (5/6) and hyponatremia (4/6). Cell content and protein yields were normal or slightly increased in the CSF of 6 patients, excluding one episode of significant increase in cell number. Patients were treated with corticosteroids, antivirals, and antibiotics, resulting in their full clinical recovery. SCC lesions mostly disappeared in all patients. Conclusion: In our study, the clinical features identified in all affected patients were mostly identical, which consisted of relatively mild CNS manifestations with a promising prognostic status.