Children with sequelae of perinatal hypoxic-ischemic encephalopathy (HIE) occasionally suffer from cytokine-related disease. We investigated 12 children with perinatal HIE sequelae, who died in childhood, concerning (1) the incidence of cytokine-related disease as the cause of death, and (2) the characteristics of the cytokine-related disease. Six (50%) of the 12 patients died from cytokine-related disease:two had virus-associated hemophagocytic syndrome (VAHS) ; one had acute encephalopathy;one had systemic inflammatory response syndrome (SIRS); and two had severe pneumonia/acute respiratory distress syndrome (ARDS). These six patients presented with increased liver transaminase, LDH, and CK, and decreased platelet count and albumin. This study shows the high incidence of cytokine-related disease as the cause of death in children with perinatal HIE sequelae. Further investigation is needed to clarify the pathogenesis of this disease.