Background and Aims: To what extent arterial hypoxaemia (AH) influences the neuroendocrine regulation of energy homeostasis remains unclear. We examined if AH causes anorexia subsequent to a systemic elevation in the circulating plasma concentration of peptide YY (PYY) and pancreatic polypeptide (PP). We further reasoned that these increases would be associated with an elevated regional (CSF) formation of free radicals given that hypothalamic reactive oxygen species suppress appetite through activation of satiety-promoting melanocortin neurons (Diano et al., 2011). Methods: Twenty-two subjects were randomly exposed to both 12% (normobaric hypoxia) and 21% oxygen (normoxia). Venous blood was obtained at baseline in normoxia (0h) following an overnight fast and after 8h and 15h exposure to each respective inspirate. CSF samples were obtained after 18h. Following blood sampling, participants consumed a liquid meal standardised for body mass. Plasma PYY-like immunoreactivity (PYY3-36 + PYY1-36) and PP were measured via radioimmunoassay. Serum and CSF N-tert-butyl-α-phenylnitrone spin-trapped alkoxyl radicals (PBN-OR) were determined via electron paramagnetic resonance spectroscopy. Appetite ratings were assessed using a visual analogue scale. Data were analysed using a two factor (trial x time) repeated measures analysis of variance and post-hoc Bonferroni-corrected paired samples t-tests.Results: Compared to normoxia, hunger ratings and the desire to eat decreased during hypoxia whereas satiety, nausea and thirst increased (P < 0.05). Hypoxia was associated with a progressive rise in serum and CSF PBN-OR (Table). In contrast, hypoxia did not influence plasma PYY or PP that were shown to decrease with time. Conclusions: These findings fail to support a role for altered PYY and PP as molecular mediators of appetite suppression in response to hypoxia. Further research is warranted to determine if free radicals contribute towards the anorexia associated with AH and to what extent anorectic gut hormones are indeed subject to redox-regulation.