Background: Family caregivers of high-mortality cancer patients perform vital tasks that deter from their own self-care. We aimed to determine differences in self-care behaviors by varying levels of caregiving intensity, well-being, and performance. Methods: Cross-sectional survey conducted in community settings of 8 cancer centers in AL, FL, and TN. Two-hundred and ninety-four family caregivers of Medicare beneficiaries diagnosed with pancreatic, lung, brain, ovarian, head & neck, hematologic, or stage IV cancer completed measures of self-care behaviors, including health responsibility, physical activity, nutrition, spiritual growth, interpersonal relations, stress management, and sleep; anxiety and depression; health-related quality of life (HRQoL); caregiver competence and preparedness; and decision-making self-efficacy. Results: Caregivers averaged 66 years and were mostly female (72.8%), white (91.2%), Protestant (76.2%), retired (54.4%) and patients’ spouse/partner (60.2%). Approximately half were rural-dwellers (46.9%) and had incomes <$50,000 (53.8%). The majority provided support 6-7 days per week (71%) for > 1 year (68%). Lower self-care behavior scores were associated with longer durations, higher hours, and more days/week of caregiving and with fair or poor patient health. Worse caregiver anxiety, depression, and mental HRQoL scores were significantly associated with lower scores in every self-care subdomain (all ps < .05). Nearly a quarter of respondents reported high depression scores (23%) and 34% reported borderline or high anxiety scores. Caregivers with lower competence, preparedness, and decision-making efficacy had lower spiritual growth, interpersonal relation, and stress management scores. Conclusions: Higher caregiving intensity is associated with worse caregiver self-care. Poorer self-care in all domains is associated with worse caregiver well-being. Interventions to optimize caregiver wellbeing should target all self-care behaviors and to optimize caregiver performance should target spiritual growth, interpersonal relation, and stress management self-care behaviors.