Objective: In individuals with asthma, obesity induces the production of leptin and is associated with disease severity. Our objective was to evaluate the levels of serum leptin and their effect on Th1/Th2 balance in obese and non-obese children with asthma, as well as to investigate the association between serum leptin levels and clinical outcomes. Methods: We evaluated 50 atopic children with physician-diagnosed moderate-to-severe persistent asthma and 20 controls. The children with asthma were divided into two groups, by body mass index percentile: obese (n = 25) and non-obese (n = 25). From all subjects, we collected peripheral blood samples in order to determine the levels of leptin, IFN-, and IL-4. Asthma severity was assessed by an asthma symptom score, and the results were correlated with the parameters studied. Results: Serum leptin levels were significantly higher in the obese asthma group than in the non-obese asthma group, as well as being significantly higher in the children with asthma than in the controls, whereas IFN- levels were significantly higher and IL-4 levels were significantly lower in the obese asthma group than in the non-obese asthma group. In addition, the obese asthma group showed higher asthma symptom scores and significantly lower FEV1 (% of predicted) than did the non-obese asthma group. There was a significant positive correlation between leptin and IFN- levels only in the obese asthma group. Conclusions: Although leptin is involved in the pathogenesis of asthma in obese and non-obese children, its effect is more pronounced in the former. In the presence of high leptin levels, only obese children with asthma exhibited Th1 polarization, with higher IFN- levels and greater asthma severity.