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Recently, several authors have reported cases in which children with human herpesvirus 6-induced post-transplantation acute limbic encephalitis (HHV6-PALE) developed generalized epilepsy and cognitive deterioration. Here, we report an 8-year-old boy who developed HHV6-PALE one month after receiving cord blood transplant for precursor B lymphoblastic leukemia. At the age of 9 years, a series of epileptic spasms started, and his cognitive function deteriorated. An interictal electroencephalogram showed generalized epileptic discharges. The patient was diagnosed with epileptic encephalopathy after HHV6-PALE. Although his condition did not respond to various antiepileptic drugs, ketogenic diets, or immunomodulatory therapies, it improved temporarily after ACTH therapy. Considering that the prognosis of this type of epileptic encephalopathy is devastating, elucidation of the mechanisms responsible for the development of epileptic encephalopathy and development of a new strategy for its management are urgently needed.