Asthma is a complex condition resulting from the interaction of genes and environment. Obesity is a risk factor to develop asthma and contributes to poor response to asthma therapy and severity. The aim of the study was to evaluate the effect of obesity on the expression levels of genes previously associated with severe asthma. Three groups of subjects were studied: non-obese asthmatics (NOA), obese asthma patients (OA), and non-asthmatic obese subjects (O). Previously reported overexpressed (IL-10,MSR1,PHLDA1,SERPINB2, andCD86) and underexpressed genes (CHI3L1,CPA3,IL-8, andPI3) in severe asthma were analyzed by RT-qPCR in peripheral blood mononuclear cells (PBMCs). In the overexpressed genes, obesity significantly decreased the expression ofMSR1andPHLDA1and had no effects onCD86,IL-10, andSERPINB2. In underexpressed genes, obesity did not affectPI3,CHI3L1, andIL-8and significantly reducedCPA3expression. The results of this study show that obesity should be included among the known factors that can contribute toward modifying the expression of genes associated with asthma and, in particular, severe asthma.