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This study aimed to evaluate serum brain-derived neurotrophic factor levels, stress, and quality of life in leprosy patients, and to explore their interrelations. A cross-sectional study was conducted from September 2024 to May 2025 at 3 hospitals in Medan, Indonesia, involving 45 leprosy patients aged ≥ 18 years who met inclusion criteria. Serum brain-derived neurotrophic factor levels were measured using ELISA, stress was assessed using the Perceived Stress Scale-10, and quality of life was evaluated through the WHOQOL-BREF questionnaire. Descriptive statistics, Shapiro-Wilk normality test, and Spearman's rank correlation were used for analysis. The mean serum brain-derived neurotrophic factor level was 7.38±3.37 ng/mL. Patients with multibacillary leprosy without reaction had higher brain-derived neurotrophic factor levels than those with type 1 or type 2 reactions. Stress levels were mild in 42.22% and severe in 28.89% of patients. Quality of life scores varied widely. A strong negative correlation was found between brain-derived neurotrophic factor and stress (r=-0.953, p< 0.0001), and a strong positive correlation between brain-derived neurotrophic factor and quality of life (r=0.962, p< 0.0001). These findings suggest that serum brain-derived neurotrophic factor levels are associated with psychological well-being in leprosy patients and may serve as a potential biomarker for mental health monitoring in this population.