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Caregiver burnout syndrome is a state of physical, emotional, and mental exhaustion experienced by someone who provides long-term care for a dependent person. At some point in our lives, we have likely experienced it while caring for a sick family member. This article aims to compare the impact of caregiver burnout syndrome on caregivers of people with disabilities at the Ann Sullivan Center during the 2022–2024 period to validate the effectiveness of the nursing interventions implemented. Methods: It is a mixed-methods, comparative, cross-sectional study with a non-probabilistic sample, based on convenience sampling. A population of 156 caregivers was reached in 2024. The Zarit Caregiver Burden Scale and a sociodemographic questionnaire were used as instruments. The intervention plan titled “To take care of you, I must first take care of myself” was implemented. Results: A feminization of caregiving was evident, with 92.3% of female participation. In 2024, 32.7% of female participants reported severe burden, whereas 24.3% reported mild burden. Comparatively, the prevalence of severe burden decreased relative to 2022 (38%) and 2023 (39%). In 81% of the participants, factors associated with severe burden include financial hardship and lack of time for self-care.