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Objectives: Lyme disease is the most common tick-borne disease. People seek health information on Lyme disease from YouTube TM videos. In this study, we investigated if the contents of Lyme disease-related YouTube TM videos varied by their sources., Methods: Most viewed English YouTube TM videos (n = 100) were identified and manually coded for contents and sources., Results: Within the sample, 40 videos were consumer-generated, 31 were internet-based news, 16 were professional, and 13 were TV news. Compared with consumer-generated videos, TV news videos were more likely to mention celebrities (odds ratio [OR], 10.57; 95% confidence interval [CI], 2.13-52.58), prevention of Lyme disease through wearing protective clothing (OR, 5.63; 95% CI, 1.23-25.76), and spraying insecticides (OR, 7.71; 95% CI, 1.52-39.05)., Conclusion: A majority of the most popular Lyme disease-related YouTube TM videos were not created by public health professionals. Responsible reporting and creative video-making facilitate Lyme disease education. Partnership with YouTube TM celebrities to co-develop educational videos may be a future direction., Competing Interests: CONFLICTS OF INTEREST No potential conflict of interest relevant to this article was reported.