Background and aim <p>Caregiver burden encompasses the physical, emotional, financial, and social challenges faced by individuals caring for a sick or disabled person. Spiritual well-being and social support have been identified as protective factors against psychological and physical issues, potentially alleviating caregiver burden. This study aims to explore the relationship between spiritual well-being, perceived social support, and caregiver burden among parents of children with disabilities.</p> Method <p>A descriptive-analytical study was conducted with 260 family caregivers, selected through systematic random sampling. Data were collected using a demographic questionnaire, the Novak and Gaug Caregiving Burden Scale, the Paloutzian-Ellison Spiritual Well-being Scale, and the Zimet Social Support Questionnaire. Statistical analysis was performed using IBM SPSS version 22, with significance set at <i>p</i> &lt; 0.05.</p> Results <p>Among the caregivers, 148 (61.4%) reported a high level of caregiving burden, while 81% indicated moderate spiritual well-being and 14.5% reported high spiritual well-being. A significant negative correlation was found between spiritual well-being, social support, and caregiving burden (<i>p</i> &lt; 0.05). Multiple linear regression analysis revealed that spiritual well-being (β = -0.41) and social support (β = -0.33) were the most significant predictors of caregiving burden. Additional significant predictors included social activities, underlying health conditions, age, caregiving duration, insurance coverage, and marital status (<i>p</i> &lt; 0.05).</p> Conclusion <p>The high caregiving burden observed in this population, along with the inverse relationship between social support, spiritual well-being, and caregiving burden, underscores the need for strategies to enhance social support and spiritual well-being. These factors may serve as cost-effective, accessible interventions to alleviate caregiving burden.</p>