This study investigated psychosocial experiences and coping strategies of caregivers of persons with mental illness in a psychiatric hospital in Ghana. The study adopted a qualitative design in which 20 participants (10 psychiatric nurses and 10 family caregivers) were sampled from the hospital and interviewed. Using thematic analysis, the results showed that stress was common with both psychiatric nurses and family caregivers, which impact on their physical health. Both groups of caregivers reported experiences of stigma, with psychiatric nurses being stigmatized mainly by other health workers whereas family caregivers reported stigma from the public, particularly neighbors. Coping strategies differed between family caregivers and psychiatric nurses, in that nurses mostly used avoidance strategies and humor in dealing with stress and stigma associated with their work whereas family caregivers used emotion-focused coping. The implications of these findings include the need for counseling services to help caregivers manage negative experiences and psychoeducation of caregivers on adaptive coping strategies as well as training strategies targeting the public and healthcare workers on measures to reduce the stigma associated with caring for persons with mental illnesses.