INTRODUCTION: Chronic Obstructive Pulmonary Disease (COPD) is the 3rd leading cause of death worldwide and is strongly associated with the development of cardiovascular disease (CVD). Large artery stiffening is recognized as a major CVD risk factor that contributes to diminished myocardial blood supply and reduced functional capacity, a marker of disease severity in COPD. Elevated oxidative stress plays a pivotal role in the etiology of both COPD and CVD. Apart from the body's endogenous ability to counteract oxidative stress, the consumption of exogenous antioxidants also enhances the capacity to scavenge free radicals and reduce arterial stiffness. Whether or not antioxidants can reduce arterial stiffness and improve functional capacity in patients with COPD, however, has yet to be elucidated. PURPOSE: This study sought to test the hypothesis that oral resveratrol, a powerful antioxidant, will reduce arterial stiffness and improve functional capacity in patients with COPD. METHODS: Ten patients with COPD (GOLD Stage II-IV) participated in this study and completed 6 weeks of oral resveratrol (500 mg/daily) or placebo (PLC) treatment. Arterial stiffness was evaluated via tonometry (SphygmoCor) before and after RES or PLC to assess augmentation index (AIx), AIx normalized to a heart rate of 75 beats per minute (AIx75), and diastolic pressure time index (DPTI). Functional capacity was measured via six-minute walk test to evaluate distance walked. RESULTS: A single dose of RES significantly (p<0.01) improved markers of arterial stiffness (AIx75: ∆RES=-8±2% vs. ∆PLC=-4±2%) while increasing myocardial perfusion (DPTI: ∆RES=158±79 mmHg vs. ∆PLC=-23±18 mmHg p=0.04). No changes (p=0.171) in functional capacity were observed after a single dose of RES or PLC. However, six weeks of RES significantly (p=0.01) reduced AIx75 (∆RES=-9±3% vs. ∆PLC=-3±2%), while it improved myocardial perfusion (DPTI: ∆RES=166±85 mmHg vs. ∆PLC=-36±18 mmHg; p=0.04) and distance walked (∆RES=25±13m vs. ∆PLC=-2±4m; p=0.04). CONCLUSION: For the first time, we have identified that the antioxidant resveratrol reduces markers of arterial stiffness and improves myocardial perfusion in patients with COPD. In addition, six weeks of daily intake of this natural antioxidant also improved functional capacity in this population. Future studies are warranted to investigate the long terms effects of resveratrol in cardiovascular health in patients with COPD.