Previous research on commercial determinants of health has primarily focused on their impact on non-communicable diseases. However, they also impact on infectious diseases and on the broader preconditions for health. We describe, through case studies in 16 countries, how commercial determinants of health were visible during the COVID-19 pandemic, and how they may have influenced national responses and health outcomes. We use a comparative qualitative case study design in selected low- middle- and high-income countries that performed differently in COVID-19 health outcomes, and for which we had country experts to lead local analysis. We created a data collection framework and developed detailed case studies, including extensive grey and peer-reviewed literature. Themes were identified and explored using iterative rapid literature reviews. We found evidence of the influence of commercial determinants of health in the spread of COVID-19. This occurred through working conditions that exacerbated spread, including precarious, low-paid employment, use of migrant workers, procurement practices that limited the availability of protective goods and services such as personal protective equipment, and commercial actors lobbying against public health measures. Commercial determinants also influenced health outcomes by influencing vaccine availability and the health system response to COVID-19. Our findings contribute to determining the appropriate role of governments in governing for health, wellbeing, and equity, and regulating and addressing negative commercial determinants of health.