(NOTE: This white paper is from an unfinished project. Further funding is needed to circulate the benefits assessment framework among expert stakeholders.) Assessing the public health benefits of research is difficult because benefits typically unfold over long time scales, with great uncertainty, and unevenly across the global population, and they depend upon disputable technical details of the research in question. As a result, the claimed public health benefits of human pathogen research are often vague or underspecified, complicating a comparison to risks. To aid decision-makers, we describe a framework for qualitatively estimating a research project’s maximum expected public health benefits. The framework is deliberately designed as a set of six simple yes-or-no questions that can be answered by reviewers who are not experts in the scientific field at issue. Underpinning the framework is the idea that the expected benefits of human pathogen research are larger when the pathogen (and the specific variants under study) are or will be circulating in humans and domestic animals. For example, the maximum benefits of research are larger (and tolerance for risk is therefore higher) when that research involves pathogens that are present threats to humanity, and benefits are smaller for research on pathogens that are unlikely to naturally evolve. We intend for this framework to be implemented alongside existing methods to evaluate scientific merit, biosafety risks, and biosecurity risks to strengthen the risk-benefit assessment process for pathogen research.