Asthma is a common pulmonary disease with chronic inflammation of the airways, and obesity is a chronic state of low-grade inflammation. Toll-like receptors (TLRs) are involved in the innate immune response. This study was designed to analyze whether obesity has an effect on the immune response of patients with asthma. We included obese asthmatic, obese, asthmatic, and healthy children. Biochemical and anthropometric analyses were performed. Interleukin (IL)-2, interferon (IFN) gamma, IL-4, IL-10, IL-1beta, and tumor necrosis factor alpha were measured. Peripheral blood mononuclear cells were analyzed by immunostaining with anti-TLR2 and anti-TLR9 antibodies. The data were expressed as means ± SEM or medians and percentiles. Kruskal-Wallis test and Dunn's multiple comparison test were applied. Asthmatic patients, both obese and nonobese, exhibited a mild asthma phenotype; none had infectious process, exacerbation, or acute symptoms during the 30 days before the inclusion in the study. The IL-2 and IFN-gamma levels in the obese asthmatic group were lower than in the other three groups. IL-4 levels in the obese asthmatic group were almost equal to those of the asthmatic group and more than in the other two groups, without significant difference. There were higher levels of TLR2 and TLR9 in obese asthmatic patients than in the other three groups. There is a decrease in Th1 cytokines in obese asthmatic patients, and we only found a trend to an increased Th2 profile. Patients studied do not appear to fit into any of the endotypes described until now. This is the first study showing the high expression of TLR2 and TLR9 in obese asthmatic patients. It is necessary to study other cytokines in obese asthmatic patients to see if it is possible to fit them into any of the already described endotypes or if it is a distinct endotype.