Depression is a serious public health concern and leading cause of global disability; in the U.S., it is estimated that over 35 million individuals suffer from depression. Health-related dysfunction, including impairment and poor quality of life, are often associated with depressive symptoms; however, little research has examined the interrelationships between these factors. Functional impairment, or the experience of difficulty conducting necessary activities of daily living, may contribute to emotional distress directly but may also impact perceived quality of life. Health-related quality of life (HRQL), which is conceptualized as a holistic and subjective perception of one’s physical and mental quality of life, is a wellestablished indicator of overall general health. Given the dearth of research examining the linkages between these variables, we hypothesized that greater levels of functional impairment would be positively related to depressive symptoms and that physical and mental HRQL would mediate this association, such that greater functional impairment would be associated with poorer mental and physical HRQL and, in turn, to greater depressive symptoms. Our sample (N=100; 70.3% female (N=71); 93% Caucasian (N=94); Mean Age = 42.18, SD = 12.83) was recruited from a rural, Southern Appalachian primary care clinic serving working and uninsured patients. Participants completed self-report measures: Instrumental Activities of Daily Living Scale, World Health Organization Quality of Life Scale - Brief, and the Center for Epidemiological Studies Depression Scale. Simple mediation analyses, consistent with Preacher and Hayes, were conducted covarying age, sex and ethnicity. In support of our hypothesis, the direct effect of functional impairment on depressive symptoms decreased but remained significant (DE=-1.39, SE=.66, p=.03) when mental HRQL was included as a mediator (IE lower 95% CI=-3.27, upper 95% CI=-.877), indicating partial mediation. In addition, the direct effect of functional impairment on depressive symptoms fell out of significance (DE=-1.18, SE=.33, p=.15) when physical HRQL was included as a mediator (IE lower 95% CI=-3.79, upper 95% CI=-.83), indicating full mediation. Our findings suggest that individuals experiencing functional limitations are less likely to report good mental and physical HRQL and, in turn, endorse higher levels of depressive symptoms. Our findings may have clinical implications; therapeutic enhancement of coping skills and problem-solving strategies may reduce psychological distress, whereas engagement with social and instrumental support networks may provide assistance with physical limits, thereby reducing risk for depressive symptoms in individuals experiencing functional impairment.