Oxygen (O) supplementation is commonly used to treat hypoxia in patients with respiratory failure. However, indiscriminate use can lead to hyperoxia, a condition detrimental to living tissues, particularly the brain. The brain is sensitive to reactive oxygen species (ROS) and inflammation caused by high concentrations of O, which can result in brain damage and mitochondrial dysfunction, common features of neurodegenerative disorders. Hyperoxia leads to increased production of ROS, causing oxidative stress, an imbalance between oxidants and antioxidants, which can damage tissues. The brain is particularly vulnerable to oxidative stress due to its lipid composition, high O consumption rate, and low levels of antioxidant enzymes. Moreover, hyperoxia can cause vasoconstriction and decreased O supply to the brain, posing a challenge to redox balance and neurodegenerative processes. Studies have shown that the severity of hyperoxia-induced brain damage varies with inspired O concentration and duration of exposure. Therefore, careful evaluation of the balance between benefits and risks of O supplementation, especially in clinical settings, is crucial.