Caregiving can be stressful, and older adults’ health and well-being may be impacted by the roles and responsibilities they assume as caregivers for persons with serious mental illness (SMI). This study is the first to apply the Stress Process Model of Caregiving (SPM) in an attempt to understand how mental illness stigma influences caregiver outcomes, specifically their desire to relinquish care. The intent of this study was to call attention to care relinquishment as an under-studied stress process outcome and to explore stress factors, with a focus on mental illness stigma, that contribute to SMI caregivers’ desire to relinquish care. Using convenience sampling, members of the National Alliance on Mental Illness in the eastern U.S. were invited to participate in an online survey, resulting in a sample of n = 285. Regression analysis findings suggest that caregivers’ partnership status, exposure to problematic behaviors, and perceptions of courtesy stigma predicted desire to relinquish care. Neither age nor caregiver sense of mastery moderated the relationship between perceived courtesy stigma and relinquishment desire. Perceptions of stigma were negatively associated with caregiver health, sense of mastery, and social support levels, indicating stigma’s role in the erosion of caregiver resources. This study provides information that can inform the development of educational and supportive services that may help caregivers better cope with the stressors associated with SMI caregiving. With caregiving stressors diminished, older caregivers will be able to better apply their resources toward self-care and maintaining their quality of life.