Rationale: The relationship between self-efficacy and health behaviors is well established. However, little is known about the relationship between self-efficacy and health-related indicators among patients with chronic obstructive pulmonary disease (COPD). Objectives: The purpose of this cross-sectional cohort study was to test the hypothesis that the total score and specific subdomain scores of the COPD Self-Efficacy Scale (CSES) are associated with functional capacity and quality of life in a group of patients with moderate to severe COPD. Methods: Relationships were examined in a cross-sectional study of baseline data collected as part of a randomized trial. Self-efficacy was measured using the five domains of the CSES: negative affect, emotional arousal, physical exertion, weather/environment, and behavioral. Measures of quality of life and functional capacity included SF-12: physical and mental composite scores, Chronic Respiratory Questionnaire dyspnea domain, and the 6-minutewalk test. Statistical analyses included Spearman correlation and categorical analyses of self-efficacy ("confident" vs. "not confident") using general linear models adjusting for potential confounders. Measurements and Main Results: There were 325 patients enrolled with amean age (standard deviation) of 68.5 (9.48) years, 49.5% male, and 91.69% non-Hispanic white. The negative affect, emotional arousal, and physical exertion domains were moderately correlated (range, 0.3 - 0.7) with the SF-12 mental composite score and Chronic Respiratory Questionnaire dyspnea domain. In models exploring each CSES domain as " confident" versus " not con fident " and adjusting for age, sex, race, pack-years, and air flow obstruction severity, there were multiple clinically and statistically significant associations between the negative affect, emotional arousal, and physical exertion domains with functional capacity and quality of life. Conclusions: The aggregated total CSES score was associated with better quality of life and functional capacity. Our analysis of subdomains revealed that the physical exertion, negative affect, and emotional arousal subdomains had the largest associations with functional capacity and quality of life indicators.These findings suggest that interventions to enhance self-efficacy may improve the functional capacity and quality of life of patients with moderate to severe COPD. Copyright © 2014 by the American Thoracic Society.