This cross-sectional study utilized a stress-process model to examine the impact of caregivers' (N = 82) perceptions of their relationship quality with a female family member (i.e., care-recipient) with substance-use or co-occurring substance and mental disorders on caregivers' perceived burden. Regression findings indicate that relationship quality impacts both subjective and objective burden. Higher levels of emotional support given to the care recipient by the caregiver predicted lower levels of caregiver displeasure; whereas higher levels of undermining of the care recipient by the caregiver predicted higher levels of caregiver stigma. Higher levels of emotional support received by the caregiver from the care recipient were associated with lower levels of caregiver displeasure and lower objective burden; higher levels of undermining of the caregiver by the care recipient predicted higher objective burden. Implications for practice and service delivery are presented. (Contains 1 figure and 3 tables.)