Abstract Background Family caregivers of children and youth with severe neurodisabilities that require chronic respiratory management often report a compromised quality of life. In this cross-sectional study, we used DeYoung’s (Psychol Inq 21(1): 26–33, 2010. 10.1080/10478401003648674) conceptualization of two personality metatraits, Alpha and Beta, to test their theorized role in facilitating resilience among these family caregivers. We expected higher Alpha and Beta would exhibit direct, beneficial effects on caregiver mental and physical health quality of life (QoL), and they would operate through self-reported resilience and coping to exert positive, indirect effects on caregiver QoL. Methods Family caregivers of children and youth at an outpatient chronic respiratory management clinic were informed of the study. Of the 68 who consented, 61 provided complete data on measures of personality traits, coping styles, and physical and mental health-related QoL. Factor analytic techniques verified the two personality metatraits, consistent with the DeYoung model. The metatraits were then used as predictor variables in a path model to predict physical and mental health-related QoL. Self-reported resilience and a coping variable were examined as possible mediators of the personality-QoL relationship. Results Correlational analyses isolated a coping variable that met criteria as a possible mediator. The path model exhibited good fit to the data. The Alpha metatrait—characterized by emotional stability, self-regulation, perseverance, and intrinsic motivation—was directly predictive of caregiver mental health. The Beta metatrait, reflecting a disposition for adaptive flexibility, responsiveness, and interpersonal initiative, demonstrated significant indirect effects to physical and mental health through its positive association with coping efforts to maintain social support and a sense of self. Conclusions Consistent with DeYoung’s conceptualization, higher Alpha and Beta predicted caregiver resilience, albeit through different pathways. The emotional stability, perseverance and emotional regulation associated with Alpha likely accounted for its positive association with caregiver mental health. Beta, in contrast, may operate through their adaptive flexibility, personal resourcefulness and social engagement to augment coping efforts that involve others and support family activities, which, in turn, promote their own physical and mental health. Limitations of the cross-sectional design, and potential theoretical and clinical implications of the personality metatraits and their relation to resilience are discussed.