This chapter focuses on the ethics of health systems research. It first explores the extent to which traditional bioethics principles—respect for persons, beneficence, and justice—are relevant to this growing field. It then demonstrates that, while these principles are pertinent to health systems research, they can be interpreted and applied differently relative to biomedical research. Upholding justice, for example, entails ensuring that projects not only fairly distribute benefits and burdens, but also specifically contribute to advancing global health justice. The chapter then argues that health systems research may further require the application of additional core ethical commitments to consider the full range of ethical issues arising in the field. Ethical commitments to public engagement, collaboration, and sustainability, which have been identified as core commitments of the field of health systems ethics, are suggested as necessary for responsible ethical oversight of health systems research. While the ethical issues discussed are globally relevant, the chapter assumes a deliberate (though not exclusive) focus on low- and middle-income countries (LMICs).