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Introduction: Autoimmune encephalitis refers to a group of diseases characterized by the presence of antibodies that directly attack receptors on the neuron surface and are associated with cognitive and behavioral disorders. Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor autoimmune encephalitis is very rare and has been reported in only a few individual cases, with little clinical experience. Case report: We describe the clinical manifestation and disease course of the first diagnosed case of anti-AMPA receptor encephalitis at the Neurology Department of Children’s Hospital 2 in November 2020. A previously healthy 10-year-old presented with symptoms over 2 periods. During each period, the patient presented with multiple focal seizures, a cognitive-behavioral disorder, and amnesia. The brain magnetic resonance imaging (MRI) results were persistently normal. Electroencephalography (EEG) recorded many focal spikes and spike waves. Antibodies against N-methyl D-aspartate (NMDA) were not detected. Antibodies against AMPA receptors were detected in the serum and cerebrospinal fluid using an indirect fluorescent antibody test. This patient was treated with immunotherapy, including methylprednisolone and intravenous immunoglobulin (IVIG), and antiepileptic drugs, such as oxcarbazepine, topiramate, and levetiracetam. The seizures were controlled, but the cognitive-behavioral disorder was only partially resolved. Conclusion: This case report contributes to the clinical understanding of anti-AMPA receptor encephalitis disease manifestation, the response to the immunotherapy, and relapse.