Published in British Medical Journal Open, this article introduces a newly launched observational longitudinal cohort study of 330 undergraduate medical students at the University of New South Wales (UNSW). Recruited in their fourth year of study, students will undergo four annual assessments as they progress through increasingly demanding clinical training. Subjective self-report questionnaires and clinical interviews for psychiatric morbidity will complement objective measures of cognitive performance, sleep/activity patterns, autonomic and immune function via peripheral blood samples. Analyses of data will be used to determine the prevalence and severity of mental disorders, elucidate underpinning psychopathology, and examine impact performance and professional functioning.The outcomes will also inform targeted preventative and treatment strategies to enhance stress resilience in trainee doctors.