The medical internship can lead to occupational stress, which affects the physical and mental health of students and may affect their quality of life. The cross-sectional study aimed to analyze the quality of life and occupational stress in medicine students enrolled in the final year of medical internship. The convenience sample consisted of 302 students with a mean age of 25.3 ± 2.4 years from public and private universities of Santa Catarina, which responded to a self-administered questionnaire. Through descriptive and inferential statistics, it was found that the average score for quality of life of those students was much higher than the average score of occupational stress, and 80% of women had high scores (80.7%) in the social domain of quality of life. In the analysis of occupational stress, the stress level was higher in men (43.7%), concerning the control demand (authority over decisions) with 6.1%, with no significant difference in scores for quality of life and occupational stress among the sexes. In conclusion, the students achieved a very high score for quality of life, although they are subjected to high levels of stress.