Enterovirus 71 (EV71) infection can lead to devastating clinical outcomes. An appreciation of the scientific relationship between cytokine response and patient mortality may help limit the risks posed by this deadly illness. We present the results of a study that compared the cerebrospinal fluid (CSF) and serum levels of interleukin-6 (IL-6) and interleukin-1β (IL-1β) in 24 patients with EV71 infection. Cases in this study involved diverse manifestations or complications, including encephalitis, poliomyelitis-like syndrome, meningitis, and pulmonary edema. CSF levels of IL-6 in study patients were found to be consistently higher during the first 2 days of central nervous system (CNS) involvement than afterward. Compared with patients who did not have pulmonary edema, patients who experienced pulmonary edema had dramatically varied blood values, including IL-6, white blood cell counts, and glucose levels. Our findings suggest that the combination of CNS and systemic inflammatory response may trigger EV71-related cardiopulmonary collapse.