Purpose: To determine the challenges, effectiveness, level of reception and acceptance of E-learning by students (learners) and faculty (educators) in a medical college during the lockdown period of the COVID-19 pandemic. Methods: An online questionnaire-based cross-sectional study was conducted among learners and educators at AIIMS, Bhubaneswar, Odisha, India, in the month of August 2020. A total of 203 learners and 24 educators participated in the study. The link of the Google form containing the questionnaire was sent to the students and teachers, and the responses obtained were analyzed with SPSS software (version 20). Results: Two hundred three MBBS students and twenty-four faculty members participated in the study. In our study, 34.5% (n=70) learners and 62.5% (n=15) educators preferred supplementation of E-learning with conventional mode of pedagogy in the future. There was a significant correlation between the convenience and the effectiveness of E-learning. Both learners and educators considered E-learning to be moderately effective. The major problems faced by the educators while conducting online sessions were network issues, difficulty in conducting practicals, lack of controlled environment, and lack of attentiveness by the learners. More than half of the students were satisfied with the E-learning provided by the institute. Educators found E-learning to be moderately convenient, whereas they felt conventional classroom teaching is highly convenient. Conclusion: Educators and learners were quick to adapt to the online mode of learning but the shift was mired with initial challenges. There is a requirement of capacity building in terms of skill development and digital infrastructure building to ensure seamless and effective E-learning.