Abstract Background: All prevention efforts currently being implemented for COVID-19 are aimed at reducing the burden on strained health systems and human resources. There has been little research conducted to understand how SARS-CoV-2 has affected healthcare systems and professionals in terms of their work. Finding effective ways to share the knowledge and insight between countries, including lessons learned, is paramount to the international containment and management of the COVID-19 pandemic. The aim of this project is to compare the pandemic response to COVID-19 in Brazil, Canada, China, France, Japan, and Mali. This comparison will be used to identify strengths and weaknesses in the response, including challenges for health professionals and health systems.Methods: We will use a multiple case study approach with multiple levels of nested analysis. We chose these countries as they represent different continents and different stages of the pandemic. We will focus on several major hospitals and two public health interventions (contact tracing and testing). It is a multidisciplinary research approach that will use qualitative data through observations, document analysis, and interviews, as well as quantitative data based on disease surveillance data and other publicly available data. Given that the methodological approaches of the project are largely qualitative, the ethical risks are minimal. For the quantitative component, the data being used are publicly available.Discussion: We will deliver lessons learned based on a rigorous process and on strong evidence to enable operational-level insight for national and international stakeholders.