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Introduction: E-learning in medical education during the COVID-19 pandemic presents challenges for teaching staff, including technical skills, limited access to technology, and difficulty in practical sessions and clinical rotations. Objectives: This study aims to explore the challenges and barriers of e-Learning in medical education during the COVID-19 pandemic experienced by teaching staff. Methods: A cross-sectional study was conducted with the teaching staff at Al-Ghad International Colleges for Applied Medical Sciences, Saudi Arabia, during the COVID-19 pandemic. An online questionnaire to collect data; 104 participants responded to the questionnaire. The data were analyzed using (SPSS version 24). Results: The findings of this study showed that the challenges faced by the teaching staff included organizational factors, such as a lack of internet services (51% agree versus 38.5% disagree), a lack of data confidentiality (76% agree versus 24.1% disagree), and a lack of education platform technical skills (6.7% agree versus 90.4% disagree). The second reported challenge was related to the student evaluation mechanisms, such as a lack of monitoring the progress of skills (86.5% agree and 4.8% disagree) and a lack of performing practical skills (93.3% versus 0 disagree). The third challenge was related to the educational platform, with 86.5% agreeing that there is a lack of monitoring of the progress of the skills domain, 70.2% agreeing there is ineffective communication, and 86.4% agreeing that there is weak active interaction. Conclusions: Our study found three main challenges of e-learning experienced by the teaching staff during the spread of the pandemic: organizational factors, student evaluation mechanisms, and educational platforms. These challenges have been experienced during the transition to e-learning. [ABSTRACT FROM AUTHOR]