This study examines academic burnout syndrome and its relation to personal and academic variables among university students in nursing and early childhood education programs in Spain. A total of 606 university students (primary education: 49.7%; nursing: 49.7%) of both sexes (71.5% female) with an average age of 20.68 years (SD = 1.65) participated. An ex post facto retrospective single-group design was planned. The instruments used were the Maslach Burnout Inventory-Student Survey (MBI-SS) and the NEO Five-Factor Inventory (NEO-FFI). Nursing students, who reported more study hours, less sleep, and lower grades, had higher academic burnout scores. Linear regression models were proposed to analyze the relationship between academic burnout, personality, and sociodemographic variables. Nursing students scored higher in emotional exhaustion and lower in cynicism, and they scored higher in neuroticism and openness. Furthermore, 16.1% of the variance in academic burnout was explained by personality variables as well as the degree studied, course year, and study hours. These findings suggest the importance of considering both academic and personality variables in understanding academic burnout in university students.