To examine the relationship between caregiving burden and parenting stress in caregivers of children with esophageal atresia and to identify factors associated with caregiving burden. Additionally, it explores whether self-efficacy mediates this correlation. An analytical cross-sectional study. Data were collected from 139 caregivers using the Zarit Caregiving Burden Scale (ZCB), Coping Self-Efficacy Scale (CSE), and Parental Stress Scale (PS) between June and October 2023. Statistical analyses included structural equation modeling and logistic regression using IBM SPSS 28.0, SPSS Amos, and Jamovi software. Among the participants, 68.3 % experienced a moderate-to-high caregiving burden. A statistically significant negative correlation was found between ZCB and CSE scores, while a moderate positive correlation was observed between ZCB and PS scores. Parenting stress was associated with caregiving burden; however, self-efficacy did not mediate this relationship. Caregivers, particularly mothers with high parental stress, a history of miscarriage, and a gestational age above 30 weeks, should be prioritized for interventions addressing caregiving burden. Assessing caregiving burden and stress in outpatient clinics is critical for effective home care management. Standardized discharge education and psychosocial support should be provided to caregivers to alleviate their burden. This study fills a research gap regarding caregivers of children with esophageal atresia and provides guidance for healthcare professionals, hospital administrators, and policymakers. Promoting community-based and personal care support services is essential for reducing caregiving burden and parental stress. This study adhered to the STARD guidelines. No patient or public involvement.