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Heart failure (HF) is a major health problem in the United States, affecting 5.7 million American adults. Psychosocial distress, in particular depression, contributes to morbidity and mortality in patients with HF. Little is known about the interrelationship among disease severity, social support, and depression.The aim of this study was to examine the contributions of social support and disease severity to longitudinal changes in depression and anxiety of outpatients with HF.Patients (N = 108) enrolled in the Psychosocial Factors Outcome Study completed the Beck Depression Inventory-II, the State Trait Anxiety Inventory, and the Social Support Questionnaire-6 at study entry and every 6 months for up to 2 years.At baseline, 30% of the patients were depressed and 42% were anxious. Social support amount contributed to changes in depression (P = .044) but not anxiety (P = .856). Depression increased over time for patients who had lower initial social support amount. Depression did not increase for those with higher initial social support amount. Neither New York Heart Association class nor treatment group (placebo or implantable cardioverter defibrillator) interacted with time to predict depression, which indicates that changes in depression were parallel for patients with New York Heart Association class II and class III HF and for those who received implantable cardioverter defibrillators and those who did not. Assessment of patients with HF should include depression and social support. Interventions to enhance social support among patients with HF who have low social support may help alleviate the development of depression.Reducing psychological distress and increasing social support may improve health outcomes among HF outpatients. It is important for studies of HF to include assessment of depression, anxiety, and social support and evaluate their contributions to health outcomes.