Background: Corona Virus Disease 2019 (COVID-19) is a global pandemic still at large whose vaccination is in a trial phase. Dental practitioners are at high risk of exposure to this deadly epidemic. Therefore, the purpose of this study is to assess the knowledge and practice of dentists in the city of Multan, Pakistan. Method: This cross-sectional study was carried out in Multan, Pakistan from January to March 2021. A 30 items valid and reliable self-administrative questionnaire was used to assess the knowledge, practice, and source of information regarding the COVID-19 pandemic from dentists. Result: The results showed that the majority of dentists practicing in Multan had good knowledge (97.8%) and more than half of the respondents had good practice (65.6%). The most common source of their knowledge was WHO and Television. Almost half of the respondents showed fear of this virus in their practices. Conclusion: Dental practitioners of Multan revealed good knowledge regarding COVID-19. However, some key points were lacking in their knowledge and practice. Our findings have important implications for developing strategies that will improve the knowledge and practices of dentists in this region and also in whole country. Keywords: COVID-19, Coronavirus, Knowledge, Awareness, Dentists, Multan.