Objective: To assess the severity and predictors of fatigue in ANCA-associated vasculitis (AAV), and the contribution of peripheral and central mechanisms. Methods: Fatigue, anxiety/depression, sleep quality and pain were measured in 152 patients with AAV, 68 patients with CKD, andTl healthy conffols. Muscle mass, strength and endurance, cardio-respiratory fitness, perception of exertion, high-sensitivity C-reactive protein (hsCRP), and dehydroepiandrosterone (DHEA) were measured in 48 patients with AAV and 4l healthy controls. Results: Fatigue in AAV was more severe than in CKD 1p:g.gl3) or controls (p<0.001), and correlated with anxiety/depression, sleep quality and pain (all p<0.001). There was no difference in muscle mass (p:0.979) or strength (p=0.315) between AAV and conhols, but muscle endurance time was shorter in AAV (p=0.006), with greater muscle reserve (p=0.038) indicating central activation failure. Perception of exertion (p=0.006) and cardio-respiratory fitness (p:0.029) were worse in AAV than controls. Only perception of exertion independently predicted AAV fatigue (p:0.01). Sleep disturbance predicted altered perception of exertion (p:0.017). hsCRP was higher (p0.01 1) and DHEAS levels were lower (p<0.001) in AAV than controls, but neither predicted fatigue. Conclusion: Fatigue in AAV is more severe than in CKD or health, is due to central mechanisms, and may be amenable to intervention.