AbstractAlthough training under intermittent hyperoxia has been shown to improve exercise performance, its effect on well‐trained mice remains undetermined. Voluntary run for 7 weeks increased maximal work values by 7.4‐fold (Bayes factor, BF ≥ 30). Subsequently, mice underwent 4 weeks of treadmill training with (INT) or without (ET) intermittent hyperoxia (30% O2). INT training significantly increased maximal exercise capacity compared to ET (BF ≥ 30). INT group exhibited significantly higher levels of cytochrome‐c‐oxidase (COX) in soleus muscle (SOL, BF ≥ 3.0). Additionally, INT enhanced 3‐hydroxyacyl‐CoA‐dehydrogenase (HAD) levels in white gastrocnemius (Gw) and plantaris (PL) muscles compared to ET (BF ≥ 3.0). Pyruvate dehydrogenase complex (PDHc) levels were significantly higher in the INT group compared to the ET group in red gastrocnemius and left ventricle (BF ≥ 30). Capillary‐to‐fiber ratio (C/F) was significantly higher in the INT group than in the ET group in SOL and PL muscles (BF ≥ 3.0). COX, PDHc, capillary density (CD), and catalase protein values in SOL, HAD, and C/F levels in Gw and PL, as well as CD values in Gw showed a significant positive correlation with maximal work values using data from ET and INT groups (p < 0.05). These findings suggest that training under intermittent hyperoxia promotes endurance performance probably by improving metabolic enzyme levels and capillary profiles in well‐trained mice.