Abstract Acute exposure to hypoxia decreases insulin sensitivity in healthy adult humans; the mechanism is unclear, but increased activation of the sympathetic nervous system may be involved. We have investigated the hypothesis that short‐term sympathetic inhibition attenuates hypoxia induced insulin resistance. Insulin sensitivity (via the hyperinsulinaemic euglycaemic clamp) was determined in 10 healthy men (age 23 ± 1 years, body mass index 24.2 ± 0.8 kg m−2 (means ± SEM)), in a random order, during normoxia (= 0.21), hypoxia (= 0.11), normoxia and sympathetic inhibition (via 48 h transdermal administration of the centrally acting α2‐adrenergic receptor agonist, clonidine), and hypoxia and sympathetic inhibition. Oxyhaemoglobin saturation (pulse oximetry) was decreased (P < 0.001) with hypoxia (63 ± 2%) compared with normoxia (96 ± 0%), and was unaffected by sympathetic inhibition (P > 0.25). The area under the noradrenaline curve (relative to the normoxia response) was increased with hypoxia (137 ± 13%; P= 0.02); clonidine prevented the hypoxia induced increase (94 ± 14%; P= 0.43). The glucose infusion rate (adjusted for fat free mass and circulating insulin concentration) required to maintain blood glucose concentration at 5 mmol l−1 during administration of insulin was decreased in hypoxia compared with normoxia (225 ± 23 vs. 128 ± 30 nmol (kg fat free mass)−1 pmol l−1 min−1; P= 0.03), and unchanged during normoxia and sympathetic inhibition (219 ± 19; P= 0.86) and hypoxia and sympathetic inhibition (169 ± 23; P= 0.23). We conclude that short‐term sympathetic inhibition attenuates hypoxia induced insulin resistance.