Background: Epidemiologic studies have shown associations between traffic-related pollutants such as diesel particulate matter (PM) and asthma outcomes in children, but the inflammatory features associated with diesel PM exposure in children with asthma are not understood.Objective: This study examined symptoms, exacerbations, and lung function measures in children with uncontrolled asthma and their associations with residential proximity to major roadways. Biomarker studies were performed to determine associations between diesel PM exposure and systemic inflammatory cytokines, circulating markers of T-cell activation and exhaustion, and metabolomic features.Methods: Children 5 through 17 years of age with physician-diagnosed, uncontrolled asthma despite treatment with an asthma controller medication completed a research visit involving questionnaires, lung function testing, and venipuncture for biomarker studies. Geocoding was performed to quantify residential proximity to major roadways and pollutant exposure.Results: Four hundred forty-seven children with uncontrolled asthma were enrolled. Children living closer to highly trafficked roadways were more disadvantaged and had more exposure to diesel PM, more exacerbations prompting an emergency department visit, and lower lung function measures. Children with the highest diesel PM exposure, compared to children with the lowest diesel PM exposure, also had blunted cytokine secretion and evidence of T cell exhaustion, as well as disturbances in several metabolites associated with glutathione formation and oxidative stress.Conclusion: Traffic-related diesel PM exposure in children with poorly controlled asthma is associated with poorer clinical outcomes and unique patterns of inflammation and oxidative stress. These findings argue for continued mitigation efforts to improve traffic-related air quality and health equity in children with asthma.