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Introduction: Most children with medical complexity have to live with home mechanical ventilation (HMV). Undertaking the care of a child with HMV creates a psychosocial burden on parents. This study investigated the impact of selected potential determinants on the quality of life of parents who have children with HMV., Methods: A cross-sectional survey study was conducted using a structured questionnaire to determine the sociodemographic characteristics of the parents. The World Health Organization Quality of Life Assessment-Brief version, the Beck Depression Inventory (BDI), and the Multidimensional Scale of Perceived Social Support were applied., Results: A total of 35 participants responded to the questionnaires. Paired data from mothers and fathers were obtained from 12 families. A moderately significant positive correlation was found between the perceived social support levels of the parents and all domains of the quality of life scale (for the physical domain: r = .455, p = .006; for the psychological domain: r = .549, p = .001; for the social domain: r = .726, p = .000; and for the environment domain: r = .442, p = .008). A moderate negative relationship was found between parents' perceived social support levels and BDI scores (r = -.557, p = .001). The multivariate regression analysis determined that being a mother, quitting a job to become a caregiver, being the only caregiver at home, and having a neurological/neuromuscular disease as the primary disease of the child were associated with lower scores in more than one quality of life domain., Conclusion: Our results emphasize that appropriate social support is important for improving the quality of life scores of parents of children with HMV., (© 2023 Wiley Periodicals LLC.)