© 2018 Iyer et al. Background: Social isolation is a common experience in patients with COPD but is not captured by existing patient-reported outcomes, and its association with clinical outcomes is unknown. Methods: We prospectively enrolled adults with stable COPD who completed the University of Alabama at Birmingham Life Space Assessment (LSA) (range: 0–120, restricted Life-Space mobility: ≤60 and a marker of social isolation in older adults); six-minute walk test (6MWT), and the University of California at San Diego Shortness of Breath Questionnaire, COPD Assessment Test, and Hospital Anxiety and Depression Scale. The occurrence of severe exacerbations (emergency room visit or hospitalization) was recorded by review of the electronic record up to 1 year after enrollment. We determined associations between Life-Space mobility and clinical outcomes using regression analyses. Results: Fifty subjects had a mean ± SD %-predicted FEV 1 of 42.9±15.5, and 23 (46%) had restricted Life-Space mobility. After adjusting for age, gender, %-predicted FEV 1 , comorbidity count, inhaled corticosteroid/long-acting beta 2 -agonist use, and prior cardiopulmonary rehabilitation, subjects with restricted Life-Space had an increased risk for severe exacerbations (adjusted incidence rate ratio 4.65, 95% CI 1.19–18.23, P=0.03). LSA scores were associated with 6MWD (R=0.50, P>0.001), dyspnea (R=-0.58, P>0.001), quality of life (R=-0.34, P=0.02), and depressive symptoms (R=-0.39, P=0.005). Conclusion: Restricted Life-Space mobility predicts severe exacerbations and is associated with reduced exercise tolerance, more severe dyspnea, reduced quality of life, and greater depressive symptoms.