We aimed to assess the kinetics of the release of proinflammatory cytokines and to clarify clinical usefulness as an indicator of the disease activity in human parechovirus type 3 virus (HPeV3)-induced sepsis-like syndrome. We measured serum levels of neopterin, interleukin (IL)-6 and the soluble forms of tumor necrosis factor (TNF) receptor types I (sTNF-RI) and II (sTNF-RII). Serum samples were obtained from 12 patients with HPeV3-induced sepsis-like syndrome and 28 healthy children. Disease course after onset was divided into 3 phases: early (day 1-2), peak (day 3-6) and recovery (day 9-16) phases. Serum IL-6 levels rapidly and markedly elevated in early phase and gradually decreased to those in healthy children in recovery phase. Furthermore, serum neopterin, sTNFR-I and sTNFR-II levels increased rapidly and markedly in onset phase and remained elevated in peak phase. These levels gradually decreased in recovery phase. Serum IL-18 levels increased from onset phase to peak phase and decreased in recovery phase. These results indicate that proinflammatory cytokines, in particular, interferon gamma, TNF-α and IL-18 are closely related to the development of HPeV3-induced sepsis-like syndrome. Serum levels of these cytokines might be a useful indicator of the disease activity.