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Background: Since millions of Muslims visit the Holy Mosque in Makkah, it is essential to highlight that such mass gatherings carry a risk of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) transmission. In this study, we assessed the level of knowledge and practices among visitors to the Holy Mosque related to the coronavirus disease 2019 pandemic. Methods: A cross-sectional survey of Holy Mosque visitors was conducted in Makkah from January 19, to February 9, 2020, using a self-administered electronic questionnaire. Knowledge and practices scores were compared and multiple logistic regression analysis was used to identify the association between variables. Results: A total of 451 participants were interviewed, while 413 completed the questionnaire and were eligible for inclusion. The range of correct answer rate was 13.1%–93.5%. The mean knowledge score was 11.3 with a 64.9% correct response rate, while the mean practices score was 2.92 with a 73.2% correct response rate. The knowledge score was significantly different among nationalities and education levels (P < 0.05). A higher level of education was associated with better knowledge regarding SARS-CoV-2 (odds ratio 1.18, P = 0.028). Conclusions: Most of the visitors to the Holy Mosque had an appropriate level of knowledge and practices related to SARS-CoV-2 infection; however, there is room for improvement in some areas.