Sleep impairments for caregivers are multifactorial. Assumptions are that caregivers of those with primary malignant brain tumors (PMBT) are similar to caregivers of persons with dementia as cognitive impairments are present at diagnosis. The shorter trajectory of PMBTs and rapid deterioration of recipients’ health may influence sleep in caregivers of persons with a PMBT. The purposes of this study were to use a sleep impairment model to characterize caregiver sleep using objective and subjective measures, and to examine sleep loss effects on psychosocial and physiologic health outcomes. A secondary data analysis using baseline data from a larger study of mind-body interactions in caregivers of family members with PMBTs was used. Caregiver data included standardized questionnaires, serum blood draw, and three-day sleep-wake activity data from an accelerometer. Analyses included descriptive statistics, correlations, t-tests, and hierarchical regression models. Caregivers (N = 133) were White (94%), female (69.2%) spouses (75.2) and on average 52 years old (SD = 11.8). Care recipients were mainly White males of similar age with a highly malignant glioma (57.4%). Sleep latency was longer (35 min, SD = 34.5), with shorter total sleep time (TST) (357 min, SD = 84.6) and more frequent wake after sleep onset (WASO; 15.1%, SD = 9.2) than in the general population. Caregivers reported high anxiety (59.4%). Caregiver comorbidities and care recipient functioning explained higher perceptions of health (R2 = 26, F(2, 84) = 14.94, p < .001). Whereas, longer TST, more WASO and poorer sleep quality explained poorer quality of life (R2 = .27, F(4, 66) = 6.19, p < .001). Sleep loss variables explained little variance in physical health status, interleukin-1ra and interleukin-6 levels, fatigue, depressive symptoms, spiritual health, social support, and work limitations. Nurses need to assist caregivers with anxiety management and ways to improve sleep at time of PMBT diagnosis. Sleep impairments place these caregivers at risk for physical and mental health problems, and compromise their ability to continue in the role.