COVID-19 pandemic is a global public health emergency that has greatly impacted the health systems and people‟s lives worldwide. With its relatively high rate of infection and mortality, COVID-19 can worsen the feelings of anxiety and stress among Healthcare Workers (HCWs). The aim of this survey was to assess the prevalence of health workforce burnout during the COVID-19 response in Ethiopia. The study employed a health institution-based qualitative, cross-sectional survey with a structured design based on the validated tool MBI-HSS (Maslach Burnout Inventory Human Services Survey). In this study, we purposively selected 824 (74%) numbers of health care workers at the accessed health facilities from 1120 at the time of the survey and a response rate of 767 (93%). The English questionnaire was translated into two local languages (Amharic and Oromffa) and the data collector were selected from each region and city and then trained for 5 days. The study revealed that the magnitude of burnout was 70 % among HCWs working in COVID-19 response that participated in the study. The prevalence of burnout among the HCWs was 58%, 68%, and 64% for moderate to high burnout on Depersonalization, Personal Accomplishment, and on Emotional Exhaustion respectively. The prevalence of burnout among HCWs increased, particularly for those who were serving longer in all survey areas. The result of the study indicated the need to identify and eliminate burnout among HCWs in order to activate psychological resilience and guide workers in the use of the most effective long-term coping strategies to protect their mental health and align the design of intervention in all COVID-19 response areas.