Objectives: The present study examined the relationship between medical student fatigue with psychological variables: emotional intelligence (EI), sense of coherence (SoC) (comprehensibility, manageability, and meaningfulness), quality of life (QoL), stress, and satisfaction with studying medicine. Material and Methods: The sample consisted of 566 medical students from the Medical University of Gdańsk, Poland. The instruments used were the Chalder Fatigue Scale, Schutte Self Report Emotional Intelligence Test, Sense of Coherence Questionnaire, and a questionnaire designed by the authors, comprised questions relating to the quality of life, stress levels, and satisfaction with studying medicine. Results: The results show that fatigue was negatively related to the ability to use emotions effectively in the management of one’s activities (EI), 1 aspect of SoC – a level of comprehensibility, QoL, and satisfaction with studying medicine. Fatigue is positively related to the ability to recognize, understand, and control emotions (EI) and stress connected with studying medicine. Conclusions: The outcomes of the study afford a better understanding of the relation- ship between selected variables in the field of individual differences in the context of fatigue in the medical student population. It may help medical educators and authorities to have a better understanding of the phenomenon of building resilience and increasing abilities to cope with the negative effects of chronic stress such as fatigue in the population of medical students. Early recognition of specific psychological features in medical stu- dents, such as misunderstanding emotions and their perception of environments as unstructured, would make it possible to prepare early support and development programmes. Int J Occup Med Environ Health. 2023;36(4):517–25