Background: Since 1998, Taiwan has experienced several hand, foot, and mouth disease (HFMD) epidemics caused by enterovirus 71 (EV71). Two notable features of severe EV71 infection in young children are brainstem encephalitis (BE) and fatal pulmonary edema (PE). This study investigated the specific immunoregulatory characterizations of EV71 neurological complications according to the disease severity. Methods: Patients younger than 18 years with virologically confirmed EV71 infections were enrolled and divided into 2 groups: the HFMD or BE group, and the autonomic nervous system (ANS) dysregulation or PE group. Laboratory findings, cytokine and cyclic adenosine monophosphate (cAMP) levels, immunophenotypes, and the regulatory T cell (Tregs) profiles of the EV71-infected patients were determined. Results: Patients with ANS dysregulation or PE exhibited a significantly low frequency of CD4⁺CD25⁺Foxp3⁺ and CD4⁺Foxp3⁺ T cells compared with patients with HFMD or BE. The expression frequency of CD4^-CD8^- was also significantly decreased in patients with ANS dysregulation or PE. Among patients with ANS dysregulation or PE, the expression frequency of CD4⁺Foxp3⁺ increased markedly after milrinone treatment, and was associated with a reduction of plasma levels IL-6, IL-8 and IL-10. Plasma concentrations of cAMP were significantly decreased in patients with ANS dysregulation or PE compared with patients with HFMD or BE, however, cAMP levels increased after milrinone treatment. Conclusions: These findings provided new insight into the role of regulatory T cells. Furthermore, CD4⁺CD25⁺Foxp3⁺ and cAMP expression might be related to the progression of severe EV71 infection, and its responses to milrinone treatment.