Purpose: The burden of caring for a family member or friend can have a negative impact on caregiver health and well-being, yet caring can also have positive consequences. Understanding the factors that may enhance caregiver well-being is merited. Methods: We used data gathered from the European Quality of Life Survey (EQLS). Using complete case analysis followed by multiple imputation analysis, a series of multilevel regression models were developed to systematically explore the role of three distinct blocks of factors in predicting caregiver well-being as measured by the WHO-5 well-being index: (1) sociodemographic and health factors, (2) care and burden-related factors, and (3) psychological and social appraisals. Differences between frequent caregivers and the general population were also compared on all measures. Results: 36,908 respondents took part in EQLS, with 4171 (11%) identifying as frequent carers. While frequent caregivers reported lower well-being compared to the remaining population, most were happy with the amount of time spent caring. Our model explained approximately 32% of variance in well-being scores. After examining the role of known risk factors, all positive psychological appraisals were associated with higher well-being (p < .001). In order of magnitude these were optimism, perceived autonomy, sense of purpose, resilience, and perceived levels of social inclusion. Self-rated health was the strongest predictor of well-being while female carers and those with high levels of various burden measures reported lower well-being. Conclusions: Findings suggest that caregiver well-being is influenced by more than simply the burden of care. As well as attempting to reduce burden, interventions aimed at supporting caregivers could focus on fostering more positive appraisals to enhance well-being in this group.