This study assessed the influence of burnout dimensions and sleep difficulties on the quality of life among preclinicalphase medical school students. Data were collected from 193 students through their completion of the World Health Organization Quality of Life Instrument, the Maslach Burnout Inventory-Student Survey, the Mini-Sleep Questionnaire, the Social Readjustment Rating Scale, and the Beck Depression Inventory. This survey performed hierarchical multiple regressions to quantify the effects of emotional exhaustion, cynicism, academic efficacy, and sleep difficulties on the physical, psychological, social, and environmental components of an individual's quality of life. The influence of confounding variables, such as gender, stress load, and depressive symptoms, were controlled in the statistical analyses. Physical health decreased when emotional exhaustion and sleep difficulties increased. Psychological wellbeing also decreased when cynicism and sleep difficulties increased. Burnout and sleep difficulties together explained 22 and 21 % of the variance in the physical and psychological well-being, respectively. On the other hand, physical health, psychological well-being, and social relationships increased when the sense of academic efficacy increased. Physical and psychological well-being are negatively associated with emotional exhaustion, cynicism, and sleep difficulties in students in the early phase of medical school. To improve the quality of life of these students, a significant effort should be directed towards burnout and sleep difficulties.