IntroductionDecades of research demonstrate that First Nations, Metis and Inuit (FN/M/I) populations have differential access to diagnostic and therapeutic healthcare. Emerging evidence shows that this continues to be the case during the SARS-CoV-2 pandemic. In an effort to rectify these differences in access to care, our team, which is co-led by FN/M/I partners, will generate and distribute evidence on COVID-19 diagnostic testing and vaccination in high-priority FN/M/I populations in Manitoba, with the goal of identifying system-level and individual-level factors that act as barriers to equitable care and thereby informing Indigenous-led public health responses.Methods and analysisOur nations-based approach focuses on FN/M/I populations with separate study arms for each group. Linked administrative health data on COVID-19 diagnostic testing and vaccinations are available on a weekly basis. We will conduct surveillance to monitor trends in testing and vaccination among each FN/M/I population and all other Manitobans, map the geographic distribution of these outcomes by health region and tribal council, and identify barriers to testing and vaccination to inform public health strategies. We will follow the course of the pandemic starting from January 2020 and report findings quarterly.Ethics and disseminationEthics approvals have been granted by the University of Manitoba Research Ethics Board and from each of our FN/M/I partners’ organisations. Our team is committed to engaging in authentic relationship-based research that follows First Nations, Metis and Inuit research ethics principles. Our FN/M/I partners will direct the dissemination of new information to leadership in their communities (health directors, community health organisations) and to decision-makers in the provincial Ministry of Health. We will also publish in open-access journals. The study will create ongoing capacity to monitor Manitoba’s pandemic response and ensure potential health inequities are minimised, with learnings applicable to other jurisdictions where detailed administrative data may not be available.