Background: Caregivers for children with complex chronic illnesses may experience emotional and physical strain, especially as concerns attention overload and the perceptions of their own psychosocial situation. These concerns, together with the additional financial cost and the socioeconomic inequalities that arise from caregiving responsibilities, create major challenges to the health status of this population group. Methods: A prospective analytical longitudinal study will be conducted, based on an exposed cohort of adult caregivers (parents or guardians) for children with complex chronic processes, to evaluate the impact of caregiving responsibilities on the health status of this population group. Conclusions and implications: The practical implications of this study are of great significance for clinical practice. The results of this study have the potential to inform the decision-making process in the healthcare sector and guide future research initiatives. The findings of this study will provide crucial insights into the health-related quality of life of caregivers of children with complex chronic illnesses, which will be valuable in addressing the challenges faced by this population group. This information can be used to improve the availability and accessibility of appropriate health services and to facilitate the development of more equitable health outcomes for caregivers of children with complex chronic illnesses. By highlighting the extent to which this population is affected both physically and mentally, the study can contribute to the development of clinical practices that prioritize the health and well-being of caregivers in the care of children with complex chronic illnesses.