We explore the association between family caregiver depression and the quality of staff-family relationships, and we test burden as a mediator of this relationship. Using structural equation modeling, we used data from a representative sample of 932 family members from 20 nursing homes in Central New York to examine the association between staff-family relationship quality and family caregiver depression. We then tested family caregiver burden as a mediator of the relationship between staff-family relationship quality and family caregiver depression. Staff-family relationship quality, specifically perceived conflict with staff, is significantly associated with family caregiver depression. Further, caregiver burden mediates this relationship. Interventions to improve staff-family relationships may impact family caregiver depression by reducing the stress that family caregivers experience.