While an effective vaccine for the SARS-CoV-2 virus is likely many months away, development could be accelerated by conducting controlled human infection (CHI) studies - which are increasingly being considered by the scientific community due to the urgent need. In a Policy Forum, Seema Shah and colleagues outline an ethical framework for conducting CHI studies in response to the COVID-19 pandemic. In CHI studies, a small number of willing participants are deliberately exposed to infection to rapidly gather data on the efficacy of experimental vaccine candidates or treatments. Many CHI studies have a safe and successful track record in the clinical efforts to address many infectious diseases, however, they can be wrought with ethical concerns. Given the nature of the evolving global COVID-19 pandemic and its rapidly growing death toll, novel CHI studies are likely to advance, albeit amidst significant uncertainty and controversy. Here, Shah et al. apply a state-of-the-art ethical framework to address the considerations and concerns for potential novel coronavirus CHI investigations. The framework outlines the conditions under which CHI studies with SARS-CoV-2 would be ethically acceptable and provide guidance for the research community and participants considering them. Among the ethical considerations addressed in their framework, the authors argue that potential CHI studies must have sufficient social value to warrant their use and maintain reasonable risks to participants.