The COVID-19 crisis may bring lasting socioeconomic changes, also affecting science, technology and innovation (STI). This paper discusses the effects that the COVID-19 crisis could have on the future of STI and its policies, building on lessons learned from past crises, an analysis of diverse sources of early data and insights from expert discussions in international policy fora. Factors shaping the future of STI include the unequal effects of the crisis on R&D spending across sectors, the accelerated adoption of digital tools and techniques, and changes in the openness and inclusiveness of research and innovation ecosystems. The paper also explores how STI policy could experience fundamental changes as resilience, environmental sustainability and inclusiveness become more prominent objectives on policy agendas. This includes experimentation with new data and digital tools for policy purposes and unconventional policy approaches, which could spur the adoption of new and more effective STI policies.