Purpose: This review investigated medical students’ satisfaction level with e-learning during the coronavirus disease 2019 (COVID-19) pandemic and its related factors.Methods: A comprehensive systematic search was performed of international literature databases, including Scopus, PubMed, Web of Science, and Persian databases such as Iranmedex and Scientific Information Database using keywords extracted from Medical Subject Headings such as “Distance learning,” “Distance education,” “Online learning,” “Online education,” and “COVID-19” from the earliest date to July 10, 2022. The quality of the studies included in this review was evaluated using the appraisal tool for cross-sectional studies (AXIS tool).Results: A total of 15,473 medical science students were enrolled in 24 studies. The level of satisfaction with e-learning during the COVID-19 pandemic among medical science students was 51.8%. Factors such as age, gender, clinical year, experience with e-learning before COVID-19, level of study, adaptation content of course materials, interactivity, understanding of the content, active participation of the instructor in the discussion, multimedia use in teaching sessions, adequate time dedicated to the e-learning, stress perception, and convenience had significant relationships with the satisfaction of medical students with e-learning during the COVID-19 pandemic.Conclusion: Therefore, due to the inevitability of online education and e-learning, it is suggested that educational managers and policymakers choose the best online education method for medical students by examining various studies in this field to increase their satisfaction with e-learning.