This report will review what is currently known about the relationship between extended reality (XR) technologies and fatigue and provide fatigue-related considerations for the application of XR to aviation operations and research. Fatigue is a complex physiological state that results in physical and/or mental symptoms that may impact a pilot’s alertness and ability to perform operational duties. Fatigue may occur due to sleep loss, extended wakefulness, circadian phase, and workload factors. While many of these factors are dependent on sleep duration/quality or the time of day within an individual’s circadian phase, workload factors that affect fatigue are more external and related to the task at hand. Workload refers to the set of external conditions and requirements of a work system, which can affect the physiological and mental states of an individual. When incorporating XR technologies into aviation operations, such as in training, it is critical to understand how XR use may impact workload, and therefore fatigue in pilots. The fatigue-related effects of workload and other factors, such as diet or external stressors, within pilots generally is well documented. Research from other uses of XR technology, such as simulated trainings in the medical field, can provide insight into potential fatiguing effects of using these new technologies. Special considerations to aspects such as lighting, ergonomics, and mitigating eye strain will be critical in managing potential workload and fatiguing effects of XR technologies in aviation. Additionally, the controlled nature of XR technology may actually combat fatigue related symptoms related to circadian disruptions due to shiftwork. For example, controlling light conditions may be able to provide circadian-related time cues, or zeitgebers, thus promoting wakefulness. Altogether, XR technology in aviation may have unique fatigue-related considerations and more research is necessary to truly understand the impacts of this technology on performance.