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Introduction: Enterovirus 71 (EV71) infections can cause hand, foot, and mouth disease (HFMD), which is a potentially fatal illness in children. Epidemics of HFMD are seen every year globally and present an increasing threat to public health worldwide. Methodology: To identify potential severity markers for severe HFMD, laboratory findings and levels of eight serum cytokines in 143 EV71- infected patients in Beijing You'an Hospital were analyzed. Patients were grouped by disease severity: Mild (no severe complications) (n = 59), isolated isolated brainstem encephalitis (BE) (n = 47), isolated pulmonary edema (PE) (n = 12), and BE+PE (n = 25). Results: IL-8 levels peaked at day one after admission and were found to be correlated to disease severity, maximal body temperature, and length of hospital stay. Among all tested cytokines, IL-8 was correlated to only IL-6 (p = 0.010). IL-6 and IL-10 were elevated in most patients (98.6% and 70.6%), but not correlated to disease severity (both p > 0.05). IFNγ was only negatively correlated to mild cases (p = 0.025). Conclusions: IL-8 was correlated to disease severity of HFMD. IL-6 and IL-10, although elevated in most HFMD patients, were not correlated to disease severity. [ABSTRACT FROM AUTHOR]