Introduction: Various antiepileptic drugs (AEDs) can induce signs and symptoms of systemic lupus erythematosus (SLE), including phenytoin, carbamazepine, ethosuximide, primidone, and valproate. The frequency of AEDs-related drug-induced SLE is unknown and depends upon the drug use. Case: A 6-year-old girl presented with arthralgias and intermittent fever for about six months. She had a history of idiopathic childhood absence epilepsy diagnosed at the age of 5 years, not controlled on ethosuximide and lamotrigine. Lamotrigine was stopped because of its adverse effect of rash. Dose of ethosuximide has been increased because of numerous daily absence seizures, and a photosensitive of her face was observed. Titers of antinuclear antibodies (＞1:256) and anti-ds-DNA antibodies (185 IU/mL) were elevated. Histone antibody and beta 2 GPI IgG, and lupus anticoagulant were positive. Ethosuximide-induced SLE was strongly suggested because of normalization of the anti-ds-DNA antibodies levels and cessation of her symptoms after the discontinuation of ethosuximide. Levetiracetam and clobazam were successively tried; however, they were stopped due to the worsening hepatic function and ineffectiveness. We carefully started valproate of a very low-dose (2.5 mg/kg/day) and slow titration, and her seizures were completely ceased. The follow-up serum antibodies became negative without use of the immunosuppressive therapy. Conclusion: This case should alert physicians to the possibility of the serious drug-induced SLE in children taking ethosuximide. We could successfully treat the intractable absence seizures with ethosuximide-induced SLE through the careful trial of valproate at a very low-dose.