BACKGROUND: Neighborhood poverty has been associated with poor health outcomes. Previous studies have also identified adverse respiratory effects of long-term ambient ozone. Factors associated with neighborhood poverty may accentuate the adverse impact of ozone on respiratory health. OBJECTIVES: To evaluate whether neighborhood poverty modifies the association between ambient ozone exposure and respiratory morbidity including symptoms, exacerbation risk, and radiologic parameters, among participants of the SPIROMICS AIR cohort study. METHODS: Spatiotemporal models incorporating cohort-specific monitoring estimated 10-year average outdoor ozone concentrations at participants' homes. Adjusted regression models were used to determine the association of ozone exposure with respiratory outcomes, accounting for demographic factors, education, individual income, body mass index (BMI), and study site. Neighborhood poverty rate was defined by percentage of families living below federal poverty level per census tract. Interaction terms for neighborhood poverty rate with ozone were included in covariate-adjusted models to evaluate for effect modification. RESULTS: 1874 participants were included in the analysis, with mean (± SD) age 64 (± 8.8) years and FEV1 (forced expiratory volume in one second) 74.7% (±25.8) predicted. Participants resided in neighborhoods with mean poverty rate of 9.9% (±10.3) of families below the federal poverty level and mean 10-year ambient ozone concentration of 24.7 (±5.2) ppb. There was an interaction between neighborhood poverty rate and ozone concentration for numerous respiratory outcomes, including COPD Assessment Test score, modified Medical Research Council Dyspnea Scale, six-minute walk test, and odds of COPD exacerbation in the year prior to enrollment, such that adverse effects of ozone were greater among participants in higher poverty neighborhoods. CONCLUSION: Individuals with COPD in high poverty neighborhoods have higher susceptibility to adverse respiratory effects of ambient ozone exposure, after adjusting for individual factors. These findings highlight the interaction between exposures associated with poverty and their effect on respiratory health.