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Human herpesvirus-6 (HHV-6) is a common infection in childhood. This systematic review aims to assess the relationship between HHV-6 infection and seizure disorders based on available literature. MEDLINE database was searched using a search strategy. We included studies that were published after 1993 in English, and described patients with HHV-6 infection and accompanying seizure or status epilepticus. We identified 503 articles, and included 147 studies. Meta-analysis results showed a 0.21 detection rate of HHV-6 in febrile seizure patients. In the febrile seizure group (110 cases), 76 patients had simple and 34 had complex febrile seizures. Patients with "HHV-6 infection and status epilepticus" had a mean age of 16.24 months. In children with febrile illnesses, a higher index of clinical suspicion for HHV-6 infection may be required. Further studies including CSF and brain tissue may be needed to validate relationships between HHV6 infection and epilepsy. J. Med. Virol. 89:161-169, 2017. © 2016 Wiley Periodicals, Inc.