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Dufera Rikitu Terefa, Adisu Tafari Shama, Bikila Regassa Feyisa, Adisu Ewunetu Desisa, Edosa Tesfaye Geta, Melese Chego Cheme, Afework Tamiru Edosa Department of Public Health, Institute of Health Science, Wollega University, Nekemte, EthiopiaCorrespondence: Dufera Rikitu TerefaDepartment of Public Health, Institute of Health Science, Wollega University, P.O.Box=395, Nekemte, EthiopiaTel +251-922260706Email duferarikitu24@gmail.com; duferar@wollegauniversity.edu.etBackground: Ethiopia has received 2.2 million doses of COVID-19 vaccine from the COVID-19 Vaccines Global Access (COVAX) facility and planned to vaccinate 20% of its population by the end of 2021. However, evidence on the current uptake of the vaccine in our country is scanty. Therefore, this study aimed to assess COVID-19 vaccine uptake and associated factors among health professionals in Ethiopia.Methods: A national online cross-sectional E-survey was conducted on COVID-19 vaccine Uptake and associated factors among health professionals in Ethiopia from June 1 to 30, 2021. A semi-structured questionnaire was created on Google forms and disseminated online. The snowball sampling technique through the authors’ network with Ethiopian residents on the popular social media like Facebook, telegram, and email was used. Descriptive statistics were performed. Multivariable logistic regression analysis was performed using Statistical Package for Social Sciences version 25, and all variables with P-value < 0.05 and adjusted odds ratio at 95% CI were used to declare the predictors of the outcome variable.Results: A total of 522 health professionals participated in the survey, of which about 324 (62.1%) of them were vaccinated with any of the COVID-19 vaccines at least once. The study indicated that COVID-19 vaccine uptake was associated with age range from 35 to 44 years [AOR = 12.97, 95% CI: 2.36– 71.21], age beyond 45 years [AOR = 18.95, 95% CI = 2.04– 36.29], being male [AOR = 2.91, 95% CI = 1.05,8.09], being only an academician [AOR = 0.23, 95% CI: 0.10– 0.49], academicians working in University hospitals [AOR = 0.19, 95% CI: 0.05– 0.83], perceiving their family as healthy [AOR = 4.40, 95% CI: 2.21– 8.75], no history of receiving other vaccine before as an adult [AOR = 4.07, 95% CI: 2.07– 8.01] and no history of contact with confirmed COVID-19 patients or clients [AOR = 0.42, 95% CI: 0.20– 0.86].Conclusion: The study found that COVID-19 vaccine uptake among health professionals was low. This was not sufficient to achieve herd immunity as at least nine out of ten health professionals are required for herd immunity. Ages, sex, place of work, perceived family health status, previous experience of receiving a vaccine as an adult and history of contact with COVID-19 clients or patients were the factors that influence the vaccine uptake among health professionals in Ethiopia. Hence, decision makers and health managers should consider instituting mandatory vaccination for health professionals and design strategies for the provision of the vaccine.Keywords: COVID-19, vaccine, health professionals, uptake, Ethiopia