INTRODUCTION: Medical students are vulnerable to experience stress, as they are routinely confronted with stressors. Acute stress can reduce studentsʼ performance on examinations, and chronic stress can contribute to cognitive disorders. Conversely, stress coping skills can reduce traineesʼ anxiety. Thus, stress coping skills may help students manage stress effectively and better maintain clinical performance. The goal of this study was to assess the relationship between medical studentsʼ stress, workload, stress coping skills, performance-enhancing mental skills, and clinical performance during a simulated clinical scenario. METHODS: During their surgery clerkship rotation, third-year medical students participated in a simulated scenario designed to assess their ability to care for an acutely ill surgical patient. Participantsʼ physiological stress was assessed using heart rate (HR) monitors during the simulation, their perceived stress using the State-Trait Anxiety Inventory, and workload using the NASA–Task Load Index immediately after. Clinical performance was assessed using a global rating scale. Stress coping skills were also assessed. The relationship between performance, stress level, workload, and coping skills was examined. RESULTS: Forty-one third-year medical students voluntarily participated in the study. Participantsʼ clinical performance was negatively correlated with perceived stress and workload during the scenario (P < 0.05). A stepwise linear regression model revealed that higher HR was the main predictor of poorer clinical performance (P < 0.05). CONCLUSIONS: In this study, medical studentsʼ HR was associated with poorer performance during a simulated clinical scenario. Adaptive stress coping skills may allow medical students to manage stressful situations and better maintain performance.