Frailty has been recognized as a risk factor for geriatric adverse events. Little is known of the role of psychosocial factors associated with frailty in explaining negative outcomes of aging. This study was aimed at 1) evaluating the differences in psychosocial factors among robust, prefrail, and frail individuals and 2) investigating whether there was any interaction effect of frailty status with empirically identified clusters of psychosocial factors on autonomy in the activities of daily living (ADLs). Two-hundred and ten older adults (age 73±6 years, 66% women) were involved in this study. Frailty was assessed using an adapted version of the frailty phenotype. The psychosocial factors investigated were depressive symptoms using the 20-item Center for Epidemiologic Studies Depression Scale, social isolation using the Friendship Scale, and loneliness feeling using the eight-item UCLA Loneliness Scale. The autonomy in ADLs was measured with the Groningen Activity Restriction Scale. Thirty-one percent of participants were robust, 55% prefrail, and 14% frail. We performed an analysis of covariance which showed differences between robust, prefrail, and frail individuals for all the psychosocial variables: Center for Epidemiologic Studies Depression Scale, F(2, 205)=18.48, P<0.001; Friendship Scale, F(2, 205)=4.59, P=0.011; UCLA Loneliness Scale, F(2, 205)=5.87, P=0.003, controlling for age and sex. Using the same covariates, the two-way analysis of covariance indicated an interaction effect of frailty with psychosocial factors in determining ADLs, F(4, 199)=3.53, P=0.008. This study demonstrates the close relationship between frailty and psychosocial factors, suggesting the need to take into account simultaneously physical and psychosocial components of human functioning.