Providing care to a spouse can be especially challenging for older adults given their compounding stressors resulting from aging and caregiving. This cross-sectional study examines the relationships between caregiving stressors and caregiver mental health problems and the potential mediator (i.e., caregiving relationship quality) of these associations. A total of 431 Americans (≥65 years) were selected from the National Study of Caregiving. Path analysis shows that care assistance was positively associated with caregiver mental health problems, and this association was mediated by negative relationship quality (Indirect effect  =  .14, p  =  .016). Moreover, role overload was positively associated with caregiver mental health problems, which was mediated by negative relationship quality (indirect effect  =  .13, p  =  .002). Findings suggest that caregiving stressors can adversely affect mental health by exacerbating negative relationship quality. Interventions that limit negative exchanges and increase compassionate communications between older spousal caregivers and their care-receiving partners are needed.