Alem Wuneh,1 Amaha Kahsay,2 Fitiwi Tinsae,3 Fisseha Ashebir,4 Gebreamlak Giday,5 Gebremeskel Mirutse,6 Gebremedhin Gebretsadik,7 Getachew Gebremedhin,3 Haftom Weldearegay,8 Kalayou Berhe,9 Manay Woldegebriel,10 Tesfay Weldeselassie,11 Yemane Berhane,3 Zinabu Hadis6 1Health System, Mekelle University College of Health Sciences, Mekelle, Tigrai, Ethiopia; 2Nutrition and Dietetics, Mekelle University College of Health Sciences, Mekelle, Tigrai, Ethiopia; 3Nursing, Adigrat University College of Health Sciences, Adigrat, Tigrai, Ethiopia; 4Maternal and Child Health, Tigrai Regional Health Bureau, Mekelle, Tigrai, Ethiopia; 5Midwifery, Axum University College of Health Sciences, Axum, Tigrai, Ethiopia; 6Environmental and Behavioral Sciences, Mekelle University College of Health Sciences, Mekelle, Tigrai, Ethiopia; 7Midwifery, Adigrat University College of Health Sciences, Adigrat, Tigrai, Ethiopia; 8Midwifery, Mekelle University College of Health Sciences, Mekelle, Tigrai, Ethiopia; 9Nursing, Mekelle University College of Health Sciences, Mekelle, Tigrai, Ethiopia; 10Public Health, Axum University College of Health Sciences, Axum, Tigrai, Ethiopia; 11Research Monitoring, Training and Publication, Tigrai Health Research Institute, Mekelle, Tigrai, EthiopiaCorrespondence: Kalayou Berhe Tel +251 91-211-7719Email Kalushaibex@gmail.comBackground: To protect health-care providers (HCPs) from COVID-19, the WHO recommends applying basic principles of infection prevention and control measures at all health-care facilities. This study aimed to assess the knowledge, perceptions, satisfaction, and readiness of HCPs regarding COVID-19 in Tigrai, Ethiopia in 2020.Methods: This cross-sectional study was conducted from June 1 to July, 2020. Data were collected using a self-administered structured questionnaire. Multistage sampling followed by purposive sampling were used to recruit study subjects. SPSS 21 was used to compute proportions and χ2 to identify risk factors.Results: Of 765 participants, 88% had adequate knowledge, close to a third showed positive perceptions and were satisfied with their job and nearly a quarter demonstrated readiness to prevent and control COVID-19. Education, knowledge, readiness, perceptions, and job satisfaction with associated with type and readiness of health facilities.Conclusion: Despite adequate knowledge of the HCPs about COVID-19, their perceptions and job satisfaction are a concern for the health-care system. Only one in five HCPs was found to be ready to prevent and control COVID-19. Efforts should be exerted to improve perceptions, job satisfaction, and readiness of HCPs to fight COVID-19.Keywords: knowledge, perception, satisfaction, readiness of HCPs, Tigrai, Ethiopia