Aim: This study aims to determine the effect of intolerance of uncertainty, sleep quality, and social support on caregiver burden among parents of children with chronic diseases. Methods: This cross-sectional study was carried out on parents of children with chronic illnesses (n = 144), who were admitted to a medical faculty hospital in Turkey from June 2023 until June 2024. The data collection was conducted using the “Family Information Form,” the “Pittsburgh Sleep Quality Index,” the “Multidimensional Scale of Perceived Social Support,” the “Intolerance of Uncertainty Scale,” and the “Caregiver Burden Scale”. Data were analyzed using Student's t-test, one-way ANOVA, and multiple linear regression analysis. Results: Participants' mean scores were found to be 37.5 ± 14.43 on the Caregiver Burden scale, 8.37 ± 3.25 on the Pittsburgh Sleep Quality Index, 66.06 ± 13.87 on the Multidimensional Scale of Perceived Social Support, and 38.97 ± 10.25 on the Intolerance of Uncertainty Scale. Income level (β = 0.252), level of intolerance of uncertainty (β = 0.200), and the number of the child's hospitalizations in the past year (β = 0.266) were significant predictors affecting the caregiver burden. Conclusion: This study revealed that parental caregiver burden was related with intolerance of uncertainty, income status, and the number of the child's hospitalizations.