Introduction: By virtue of the nature of their work, emergency medicine physicians and residents experience high cognitive load and stress, which are known to affect physician performance and patient outcomes. However, the contribution of cognitive load has not previously been measured during the clinical work of emergency physicians. The objectives of this study were to measure cognitive load and stress in emergency physicians and residents during clinical work, evaluate the relative contribution of multiple factors on cognitive load, and to determine the effect of experience on these results. Methods: This observational study was conducted at an academic Canadian Urgent Care Centre from July to August 2018. Emergency medicine residents and staff physicians completed a survey while on shift to evaluate measures of cognitive load and acute stress. Patient acuity and the number of active patients for each physician, hours worked and patients in the waiting room were recorded. Correlational analyses and multivariable linear regression were performed to evaluate the effect of each predictor on measures of overall cognitive load. Results: A total of 131 questionnaires were completed by 42 physicians (87 questionnaires from 26 staff physicians and 44 questionnaires from 16 residents). Results showed that staff physicians carried a significantly higher patient load compared to residents (p < 0.001). There were no differences in mean overall cognitive load (p = 0.25), acute stress (p = 0.17) or measured subcomponents of cognitive load between the two groups. Perceived case difficulty and acute stress were strong predictors of overall cognitive load, while level of distraction did not correlate with the other outcomes. The number of patients in the waiting room predicted acute stress in staff physicians, while the number of higher acuity patients was a significant predictor in residents. Conclusion: Measures of overall cognitive load and acute stress were strongly correlated in the clinical setting. Different factors affect cognitive load and acute stress in staff physicians compared to residents. Appreciating these differences may help medical educators understand the cognitive challenges faced by learners in a clinical context, and aid in the design of cognitive and educational strategies to help mitigate these challenges and reduce stress.