Advances in treatment have prolonged life in heart failure (HF) patients, leading to increased attention to quality of life (QOL) and psychological functioning. It is not clear if ethnic differences exist in factors associated with psychological well-being. We examined psychosocial factors associated with depression and anxiety in 97 HF patients. Medical records were reviewed and patients (M age 53, 50% African American) completed surveys examining social support, coping, spirituality, and QOL for their association with depression and anxiety. Multiple regressions suggested that psychosocial factors were associated with psychological health. Patients with lower social support, lower meaning/peace and more negative coping reported greater depression; positive coping, and lower meaning/peace were associated with higher anxiety. Ethnicity stratified models suggested that spiritual well-being was associated with depression only among African Americans and QOL partially mediated this relationship. Findings suggest the importance of considering the unique psychosocial needs of diverse populations to appropriately target clinical interventions.