Introduction The current coronavirus disease 19 (COVID-19) outbreak has been declared to be a pandemic by the World Health Organization (WHO). It is evolving daily and has jeopardized life globally across social and economic fronts. One of the six key strategic objectives identified by the WHO to manage COVID-19 is to communicate critical information to all communities and prevent the spread of misinformation. We analyzed content on YouTube.com, a widely used web-based platform for medical and epidemiological information. Methods YouTube search results using two keywords were analyzed each in six languages - English, Arabic, Bengali, Dutch, Hindi, and Nigerian Pidgin on April 8, 2020. Forty videos in each of the six languages (i.e., a total of 240 videos) were included for analysis in the study. Two reviewers conducted independent analyses for each language. The inter-observer agreement was evaluated with the kappa coefficient (kappa). Modified DISCERN index and Medical Information and Content Index (MICI) scores were used for the reliability of content presented in the videos and information quality assessment, respectively. Analysis of variance, Kruskal-Wallis, Mann-Whitney test, and chi-square tests were done appropriately for data analysis. A p-value of less than 0.05 was considered statistically significant. All calculations were performed using SPSS Statistics for Windows, Version 21.0 (IBM Corp, Armonk, NY). Results The videos cumulatively attracted 364,080,193 views. Altogether, 52.5% of videos were Informative, 23.75% were News Updates, and 8.33% were Personal Experiences. Ten percent of videos were found to present medically misleading information. Independent Users contributed 75% of the misleading content. The overall Mean DISCERN score, an index of content reliability, was 2.62/5. The overall Mean MICI Score was 5.68/25. Videos had better scores in the Transmission component of the MICI scale and scored low on the Screening/Testing component. Conclusion The reliability and quality of the content of most videos about COVID-19 and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were found to be unsatisfactory. Videos with misleading content were found across all six languages, and sometimes garnered a higher percentage of views than those from credible sources. The share of videos contributed by Government and Health Agencies was low. Medical institutions and health agencies should produce content on widely used platforms like YouTube for quality medical and epidemiological information dissemination.