Background HF caregivers often experience caregiving burden, impacting their physical and psychological well-being. Social support and social problem-solving, as coping resources, may influence the effect of caregiving burden on self-care, depressive symptoms, and quality of life. Yet, studies examining these coping resources on HF caregiver outcomes are lacking. Purpose To investigate whether social support and social problem-solving mediate the relationships among caregiving burden, self-care, depressive symptoms, and quality of life in HF caregivers. Methods Using a descriptive, cross-sectional, correlational design, HF caregivers (n=530) completed online surveys, including the Dutch Objective Burden Inventory, the Interpersonal Support Evaluation List-12, the Social Problem-Solving Inventory Revised-Short, the Center for Epidemiological Studies - Depression scale, the Denyes Self-care Practice Instrument, and the Bakas Caregiving Outcomes Scale. Path analytic methods were used to examine a hypothesized mediating role of social support and social problem solving in the relationships between caregiving burden and caregiver self-care, depressive symptoms, and quality of life. The analysis proceeded in two phases: 1) a model-development phase with ∼62% of the sample (n=329) used to make data-based decisions on measurement indicators and structure of the path model; and 2) a confirmatory phase with ∼38% of the sample (n=201) used to provide unbiased inference on the model structure resulting from the initial phase. Results Participants were 41.39 (± 10.38) years old, Caucasian (78.3%), men (50.9%) caring for their spouse with HF (44.9%). Perceived caregiver burden was a predictor of caregiver social support (standardized effect B= -.4), self-care (Total B= -.39), depressive symptoms (Total B= .45), and quality of life (Total B= -.33). Higher level of caregiver burden was associated with less social support, worse self-care, more depression and decreased quality of life. Social support mediated the relationship between caregiving burden and depression (56% of Total effect), but did not appear to relevantly mediate the relationship between caregiving burden and self-care (11% of Total effect) or quality of life (0% of Total effect). When considered simultaneously with social support, social problem-solving was not a relevant mediator between caregiving burden and outcomes. Conclusions Caregiving burden negatively impacts caregiver outcomes. Social support appears more beneficial in mediating the effects of caregiving burden on depression, but has little mediational effect on caregiver self-care or quality of life.