The aim of this study was to investigate the relationship between burnout level and psychological resilience in parents of children with Down syndrome (DS). This study was conducted at a Special Education and Rehabilitation Center in Türkiye between August and October 2022. The sample of the correlational and cross-sectional study consisted of 80 parents of children with DS. In this study, descriptive characteristics form (DFC), Maslach Burnout Inventory (MBI), and brief resilience scale (BRS) were used to collect data. The parents' mean scores on the emotional exhaustion subscale (EES) and personal achievement subscale (PAS) of MBI according to descriptive characteristics revealed statistically significant difference in the EES and PAS scores associated with the parents' age, gender, education status, working status, number of children in the family, and family type (p < 0.05). The parents' mean scores on the BRS according to descriptive characteristics revealed statistically significant difference in BRS scores associated with the gender, educational status, working status, number of children, type of family, and presence of a chronic disease in the child (p < 0.05). There was a strong negative correlation between the EES and the BRS (r = −0.740, p < 0.05), and a strong positive correlation between the PAS and the BRS (r = 0.758, p < 0.05). It was determined that parents' emotional exhaustion levels increased as their psychological resilience levels decreased, and parents' personal accomplishment increased as their psychological resilience levels increased.