Aim: To evaluate the correlation between neurotrophin expression and clinical findings, disease severity, and outcome of children with H1N1 viral infection. Methods: Prospective observational clinical study performed on 15 children with H1N1 infection and 15 controls with lower respiratory tract infections. Neurotrophic factor Nerve Growth Factor (NGF), Brain Derived Neurotrophic Factor (BDNF), and Glial Derived Neurotrophic Factor (GDNF) plasma levels were measured using immunoenzymatic assays. Results: Significantly higher levels of BDNF and NGF were detected in patients with H1N1 infection respect to controls, while GDNF did not show significant variations in both groups. In H1N1 patients with more severe clinical manifestations BDNF and NGF levels were significantly higher respect to H1N1 patients with mild clinical manifestations. Noteworthy, NGF up-regulation was associated with duration of cough. No correlation was found between neurotrophic factor expression and final outcome. Conclusions: H1N1 infection induces an early and significantly BDNF and NGF up-regulation. The overexpression of these molecular markers, namely NGF, is likely to play a neuro-immunomodulatory role in H1N1 infection and may contribute to airway inflammation and bronchial hyperreactivity in infected children.