Summary: Hypoxia is an inherent pathophysiological characteristic of chronic kidney disease (CKD), which is closely associated with the development of renal inflammation and fibrosis, as well as CKD-related complications such as anaemia, cardiovascular events, and sarcopenia. This review outlined the characteristics of oxygen supply in the kidney, changes in oxygen metabolism and factors leading to hypoxia in CKD. Mechanistically, we discussed how hypoxia contributes to renal injury as well as complications associated with CKD. Furthermore, we also discussed the potential therapeutic approaches that target chronic hypoxia, as well as the challenges in the study of oxygen homeostasis imbalance in CKD.