Purpose: This study aimed to examine the effects of burnout, spiritual well-being, and related factors on caregiver burden in parents of children with cancer. Design and methods: This descriptive and correlational study comprised 151 parents whose children with cancer were followed up in a university hospital in T & uuml;rkiye. The data were collected through face-to-face interviews using the Maslach Burnout Inventory (MBI), Spiritual Well-Being Scale (SWBS), and Zarit Caregiver Burden Interview (ZBI). Descriptive statistics (number, percentage, mean, and standard deviation) and multiple regression analysis were used for data analysis. Results: The mean emotional exhaustion, depersonalization, and personal accomplishment subscale scores of MBI were 8.50 f 5.88 (0-24), 2.65 f 2.79 (0-13), and 24.70 f 5.20 (8-32), respectively. The mean SWBS total and ZBI scores were 126.80 f 13.13 (92-145) and 30.20 f 13.45 (4-66), respectively. More than half of the parents (53.0 %) had mild-to-moderate caregiver burden. Emotional exhaustion, depersonalization, and having a child diagnosed with leukemia were the predictors of caregiver burden, accounting for 63.9 % of the total variance. Conclusions: Emotional exhaustion, depersonalization, and having a child diagnosed with leukemia were associated with increased caregiver burden, whereas spiritual well-being decreases it. Implications of practice: Nurses should implement targeted psychosocial interventions to reduce the caregiver burden, especially for parents with children diagnosed with leukemia. In addition, they should support parents spiritually by considering their beliefs and values to further reduce caregiver burden. (c) 2025 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.