How to account for participants' psychological and emotional exhaustion with research has been under-explored in the research ethics literature. Research fatigue, as it is known, has significant impacts on patients' well-being and their ongoing and future participation in studies. From the perspective of researchers and researched communities, research fatigue also creates selection bias and opportunity costs, negatively impacting the collective scientific enterprise. Institutional Review Boards should systematically consider research fatigue during the research approval process and strive to mitigate it.