Background Self-care, a key element of heart failure care, is challenging for patients with impaired cognition. Mechanisms through which cognitive impairment affects self-care are not currently well defined but evidence from other patient populations suggests that self-efficacy, or task-specific confidence, mediates the relationship between cognitive functioning and patient behaviors such as self-care. Objective The aim of this study was to test the mediating role of self-care confidence in the relationship between cognition and self-care behaviors. Design A secondary analysis of data from a cross-sectional study. Setting Outpatient heart failure clinics in 28 Italian provinces. Participants 628 Italian heart failure patients. Methods We used the Self-Care of Heart Failure Index v.6.2 to measure self-care maintenance, self-care management, and self-care confidence. Cognition was assessed with the Mini Mental State Examination. Structural equation modeling was used to analyze the data. Results Participants were 73 years old on average (SD = 11), mostly (58%) male and mostly (77%) in New York Heart Association functional classes II and III. The mediation model showed excellent fit (comparative fit index = 1.0; root mean square error of approximation = 0.02): Self-care confidence totally mediated the relationship between cognition and self-care maintenance and management. Conclusion Cognition affects self-care behaviors indirectly, through self-care confidence. Interventions aimed at improving self-care confidence may improve self-care, even in heart failure patients with impaired cognition.