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The existence of common inflammatory biomarkers linking obesity and asthma in children has been hypothesized. Nevertheless, laboratory and clinical characteristics of children with obesity and asthma are still poorly defined. The primary aim of the present study is to investigate the lung function and the cytokine profile, in children with obesity and asthma. In this prospective, cross-sectional pilot study, pulmonary function tests, biochemical parameters, and serum cytokines levels were compared in three groups of 28 children each, matched for age and sex. Obese children showed normal forced spirometry values except an increased distal airway resistance in subjects with obesity and no asthma. Both groups including obese children showed higher leptin and IL-10 levels and lower adiponectin and TNF-alpha levels compared to children with no obesity and asthma. IL-33 and TGF-beta1 levels were higher in children with obesity and asthma vs. children with normal weight and asthma. Finally, IL-6 was undetectable in approximately 70% of obese children with no asthma, in 57% obese asthmatic children and in 100% of children with normal-weight and asthma. Children with obesity and asthma show the most striking cytokine profile, suggesting a pro-inflammatory role of fat mass in asthma development.