Background: Coronavirus (COVID-19) is posing a major and unprecedented challenge to health service planning and delivery across health systems internationally. This nationally funded study is analysing the response of the Colombian health system to the COVID-19 pandemic, drawing on qualitative case studies of three local health systems within the country. The approach will be informed by the concept of 'major system change'-or coordinated change among a variety of healthcare organizations and other relevant stakeholders- to identify processes that both enable and inhibit adaptation of health services to the challenges presented by COVID-19. The study will collect information on capacity 'bottlenecks' as well as successful practices and forms of innovation that have emerged locally, which have the potential for being 'scaled up' across Colombia's health services. Methods/design: This qualitative study will be undertaken in two phases. In the first, up to 30 stakeholder interviews will be conducted to ascertain immediate challenges and opportunities for improvement in response to COVID-19 that can be shared in a timely way with health service leaders to inform health service planning. The stakeholders will include planning, provider and intermediary organizations within the health system at the national level. In the second, up to 60 further interviews will be conducted to develop in-depth case studies of three local health systems at the metropolitan area level within Colombia. The interview data will be supplemented with documentary analysis and, where feasible, non-participant observation of planning meetings. Discussion: The study's findings will aid evaluation of the relevance of the concept of major system change in a context of 'crisis' decision-making and contribute to international lessons on improving health systems' capacity to respond to COVID-19 and future pandemics. Study findings will be shared among various stakeholders in the Colombian healthcare system in a formative and timely way in order to inform healthcare planning in response to COVID-19 and future pandemics. Conducting the study at a time of COVID-19 raises a number of practical issues (including physical distancing and pressure on health services) which have been anticipated in the study design and research team's ways of working.