Variations in oxygen availability are known to disrupt homeostatic control, and it is known that exercise in hypoxia increases cellular metabolic permutations. However, to date, the metabolomic response to exercise in hypoxia remains unknown. To examine this, 24 male participants completed one hour of exercise at a workload corresponding to 75% of pre-determined VO2peak in hypoxia (Fio2 = 0.16%), and a control repeated in normoxia (Fio2 = 0.21%), while pre- and post-exercise and 3 hour post-exercise metabolites where analysed using a LC ESI-qTOF-MS untargeted metabolomics approach in serum samples. Exercise performed in hypoxia and in normoxia independently increased metabolism as shown by a change in twenty-two metabolites associated with lipid metabolism (p<0.05, pre vs. post-exercise), though hypoxia per se did not induce a greater metabolic change when compared to normoxia (p>0.05). Recovery from exercise in hypoxia independently decreased seventeen metabolites associated with lipid metabolism (p<0.05, post vs. 3 hrs post-exercise), compared with twenty-two metabolites in normoxia (p<0.05, post vs. 3 hrs post-exercise). Twenty-six metabolites were identified as sensitive responders to exercise and recovery (pooled hypoxia and normoxia pre vs. recovery, p<0.05). These include metabolites associated with purine metabolism (adenine, adenosine and hypoxanthine), the amino acid phenylalanine, and several acylcarnitine molecules. This work demonstrates that exercise as an independent factor can activate pathways associated with lipid, protein and purine nucleotide metabolism. We conclude that exercise in hypoxia can activate metabolic pathways aligned to purine and lipid metabolism, but this effect is not selectively different from moderate exercise in normoxia.