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Larrey Kasereka Kamabu,1,2 Hervé Monka Lekuya,2 Richard Newton Iranya,2 Bienvenu Muhindo Kasusula,3 Franck Katembo Sikakulya,1,4 Saviour Kicaber,2 Moise Muhindo Valimungighe,1,5 Sifa Katungu Nganza,1,2 Eric Sadiki Butala,6 Zacharie Muhindo Sikiminywa,7 Louange Maha Kathaka,1 Dalton Kambale Munyambalu,8 Thérèse Yenyi Ahuka Longombe,9 Agnès Kavira Katsioto,1,10 Bienfait Mumbere,4 Adelard Kalima Nzanzu,1,3 Frederic Kavughe,11 Thaddée Katembo Kambere,12 Robinson Ssebuufu13 1Department of Surgery, School of Medicine, Université Catholique du Graben, Butembo, Democratic Republic of the Congo; 2Department of Surgery, School of Medicine, Makerere University, Kampala, Uganda; 3Department of Internal Medicine, Matanda Teaching Hospital, Butembo, Democratic Republic of the Congo; 4Department of surgery, Kampala International University, Western Campus, Kampala, Uganda; 5Department of General Surgery, Université d’Abomey Calavi, Cotonou, Republic of Benin; 6Department of Obstetrics and Gynecology, Consolata Hospital Mathari, Nyeri Town, Kenya; 7Department of Ophthalmology, Kinshasa Teaching Hospital, Université de Kinshasa, Kinshasa, Democratic Republic of the Congo; 8Department of Internal Medicine, Kampala International University, Western Campus, Kampala, Uganda; 9Department of Anesthesia and Critical Care, School of Medicine, University of Cheikh Anta Diop de Dakar, Dakar, Senegal; 10Department of Emergency Medicine, Alexandria University, Alexandria, Egypt; 11Department of Education and Psychology, Faculty of Education and Psychology, Adventist University of Lukanga, Lukanga, Democratic Republic of the Congo; 12Department of Public Health Sciences, Faculty of Medicine, Adventist University of Lukanga, Lukanga, Democratic Republic of the Congo; 13Uganda Medical and Dental Practitioners Council, Kampala, UgandaCorrespondence: Larrey Kasereka Kamabu, Email kamabularry@gmail.com; larry9kamabu@yahoo.frBackground: During its first wave of COVID-19 infection in sub-Saharan Africa, there was insufficient understanding of the pandemic among frontline health workers. This study was carried out to determine the knowledge, attitude, and practices (KAP) of frontline health workers (HWs) towards COVID-19 in Africa and their related factors.Methods: This was a multicenter online cross-sectional study conducted between April 2020 and July 2020 using a Google survey link among frontline HWs involved in the COVID-19 response in 26 African countries. Bivariate and multivariate logistic regression were used to analyse the determinants of KAP. Data were analyzed using STATA ver 16; all tests were two-sided with 95% confidence interval.Results: Five hundred and seventeen participated in this study from 26 African countries; 289 (55.9%) were male and 228 (44.1%) female. Most of HWs, 379 (73.3%) showed poor knowledge about COVID-19 infection and preventive measures. In contrast, majority of them showed good attitude (89%) and practice (90.3%) towards prevention of COVID-19 infections. Knowledge varied among countries; Uganda had the greatest number of HWs with good knowledge (OR: 28.09, p< 0.0001) followed by Ghana (OR=10.92, p=0.001) and DRC (OR: 4.59, p=0.015). The cadre of HWs also influenced knowledge; doctors were the most knowledgeable as compared to other cadres (OR: 3.4, p= 0.005). Attitude and practice were both influenced by HWs country of workplace and their cadre (p< 0.05).Conclusion: Majority of the frontline HWs in the African region had an overall good attitude and practice towards COVID-19 infection and practice measures despite relatively poor knowledge. The KAP is influenced by HWs country of workplace, their cadre. The knowledge of HWs in Africa should be increased to concourt with their attitude and practice to reduce the burden of intra-hospital transmission of the COVID-19.Keywords: knowledge, attitude, practices, COVID-19, frontline health workers, Africa, survey