This study determined the concentrations of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), soluble TNF receptor 1 (sTNFR1) and soluble E-selectin (sE-selectin) in cerebrospinal fluid (CSF) and serum from 15 children with influenza virus-associated encephalopathy to determine the role of cytokines in the pathogenesis. Cytokines and sTNFR1 were measured by enzyme-linked immunosorbent assay. The CSF IL-6, TNF-alpha and sTNFR1 concentrations were elevated in 9, 4 and 4 of 12 children, respectively. The serum concentrations of IL-6, TNF-alpha, sTNFR1 and sE-selectin were elevated in 10, 2, 5 and 7 of 13 children, respectively. Four children with elevated TNF-alpha and sTNFR1 levels in the CSF had neurological sequelae. The results suggested that cytokines not only in serum but also in CSF play a pivotal role in influenza virus-associated encephalopathy, and that the CSF TNF-alpha and sTNFR1 levels may be important for predicting neurological sequelae.