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Background: The COVID-19 pandemic and governments' response lead to dramatical change in quality of life worldwide. However, the extent of this change in Vietnamese medical and nursing students has not been documented., Objectives: The study aims to describe the quality of life and changes in quality of life of medical and nursing students during the COVID-19 pandemic and examine the association of quality of life and changes in quality of life with fear of COVID-19 and other socio-economic and demographic factors., Methods: The study was a cross-sectional study on all students of Hanoi Medical University from 3 majors: General Medicine, Preventive Medicine, Nursing (3672 invited students); from 7th to 29th of April 2020; using an online questionnaire that included demographic and academic information, the Vietnamese version of the SF-36 Quality of Life questionnaire and the Fear of COVID-19 Scale (FCV-19S). Linear and modified Poisson regression was used to examine the association between quality of life, changes in quality of life and other factors., Results: The number of participants was 1583 (response rate 43%). Among 8 dimensions of the SF-36 (ranged 0-100), Vitality had the lowest score with a median score of 46. The median physical composite score (PCS) of the sample was 40.6 (IQR:20.8-53.2), 33.5% of the sample had an above-population average PCS score. The median mental composite score (MCS) of the sample was 20.3 (IQR:3.8-31.7), and 98.2% had an MCS score below average. 9.9% (95%CI:8.5%-11.4%) of the population reported a significant negative change in the quality of life. Fear of COVID-19 was not associated with significant changes in quality of life, nor MCS while having some association with PCS (Coef:-5.39;95%CI:-3to-7.8). Perceived reduction in quality of life was also associated with: being on clinical rotation COVID-19 (PR:1.5;95%CI:1.05-2.2), difficulties affording health services (PR:1.4;95%CI:1.02-1.95), obesity (PR:2.38;95%CI:1.08-5.25) and chronic disease (PR:1.92;95%CI:1.23-3), typical symptoms (PR:1.85; 95%CI:1.23-2.78) and atypical symptoms of COVID-19 (PR:2.32;95%CI:1.41-3.81)., Conclusion: The majority of medical and nursing students had below average quality of life, with lower vitality and mental composite health score in the settings of COVID-19. Perceived decrease in quality of life was associated with clinical rotation, difficulties affording healthcare services and was not associated with Fear of COVID-19., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Minh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)