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Although research has emerged documenting the psychosocial impact of family care for cancer patients, few efforts capture the multi-dimensional nature of cancer caregiving stress, particularly among socioeconomically diverse samples. Utilizing data collected from cancer caregivers at a non-urban, Southern US site and an inner-city, Northeastern US site (N = 233), the present study identified predictors of multiple dimensions of caregivers' subjective stress (i.e. emotional appraisals of care demands). Various indicators representing the sociodemographic context of care, cancer care demands, and psychosocial resources were found to exacerbate or buffer caregivers from feelings of exhaustion, role entrapment, and loss of intimacy with the cancer patient. The multivariate regression model also emphasized the diffuse yet potent role care recipient mood problems and caregiver mastery/optimism have on multiple dimensions of subjective stress. The findings offer a number of recommendations for future research and practice focused on informal cancer care.