Objective: Acquired brain injury (ABI) is associated with many physical and psychiatric conditions. Oftentimes, the individual’s family members are responsible for providing long-term care, leaving caregivers vulnerable to negative effects of caregiving including stress, depression, and decreased quality of life. Attribution theory suggests that caregivers may blame the individual with the ABI for their injury as a way to understand their own circumstances. The objective of this study was to investigate caregiver coping strategies as possible mediators between caregiver family member blame and caregiver psychosocial outcomes among caregivers of individuals with ABI. Method: Caregivers of individuals with ABI (n = 94) completed an online survey of self-report measures regarding coping (emotion-focused, problem-focused, and dysfunctional strategies), blame (direct, indirect, and preoccupation with blame), depressive symptoms, and quality of life (QOL). Bootstrapping mediation analyses were conducted to investigate the mediating role of caregiver coping strategies between blame attributions, and either depressive symptoms or QOL. Results: Results demonstrated that the use of more dysfunctional coping strategies significantly mediated the relationship between indirect blame, and depressive symptoms and QOL. Furthermore, using more dysfunctional coping strategies also significantly mediated the relationship between preoccupation with blame and depressive symptoms. Conclusions: Results of this study point to the important role blame attributions play in the use of coping strategies and subsequent psychosocial outcomes. By understanding the relationships between blame attributions, coping behavior, and psychosocial outcomes, clinicians may better tailor treatments to optimize QOL and promote the psychological well being of caregivers and care recipients.