Background: Caregivers of children with cystic fibrosis (CF) are at risk for psychosocial difficulties, which has been related to poorer child well-being and medical adherence. Methods: The present study utilized the National Survey of Children's Health (NSCH) to examine self-reported differences in caregiver functioning among a matched sample of caregivers of youth with CF, asthma, and healthy controls (N = 114). Results: CF caregivers reported poorer mental health and more parenting aggravation. Among CF caregivers, poorer caregiver mental health predicted less family resilience, which in turn, predicted more parenting aggravation. Conclusions: Findings have implications for prevention screening and brief interventions within pulmonary medicine.