Hypoxic modulation of nitric oxide (NO) production pathways in the cutaneous microvasculature and its interaction with cold-induced reflex vasoconstriction, independent of local cooling, has yet to be identified. This study assessed the contribution of NO to non-glabrous microvasculature perfusion during hypoxia and whole-body cooling with concomitant inhibition of NO synthase (NOS; via L-NAME) and the nitrite reductase, xanthine oxidase (via allopurinol), two primary sources of NO production. Thirteen volunteers were exposed to independent and combined cooling via water perfused suit (5ºC) and normobaric hypoxia (FO, 0.109 ± 0.002). Cutaneous vascular conductance (CVC) was assessed across four sites with intradermal microdialysis perfusion of 1) Lactated Ringers solution (control), 2) 20 mmol L-NAME 3) 10 µmol allopurinol, or 4) combined L-NAME/allopurinol. Effects and interactions were assessed via 4-way repeated measures ANOVA. Independently, L-NAME reduced (43%, p < 0.001), while allopurinol did not alter CVC (p = 0.5). Cooling decreased CVC (p = 0.001) and the reduction in CVC was consistent across perfusates (~30%, p = 0.9). Hypoxia increased CVC (16%, p = 0.01), with this