Adipose tissue (AT) oxygen tension (pO2) has been implicated in AT dysfunction and metabolic perturbations in both rodents and humans. Compelling evidence suggests that hypoxia exposure alters metabolism, at least partly through effects on AT. However, it remains to be elucidated whether mild intermittent hypoxia (MIH) exposure impacts the AT proteome. We performed a randomized, single-blind, cross-over study to investigate the effects of seven consecutive days of MIH (FiO2 15%, 3x2h/d) compared to normoxia (FiO2 21%) exposure, on the AT proteome in overweight/obese men. AT insulin sensitivity was determined by a two-step hyperinsulinemic-euglycemic clamp, and abdominal subcutaneous AT biopsies were collected (n=11) under normoxic, fasting conditions following both exposure regimens. AT proteins were isolated and quantified using liquid chromatography-mass spectrometry. After correction for blood contamination, 1022 AT protein IDs were identified, of which 123 were differentially expressed following MIH (p < 0.05). These proteins were involved in redox systems, cell-adhesion, actin cytoskeleton organization, extracellular matrix composition and energy metabolism. We demonstrate for the first time that MIH exposure impacts the AT proteome. Moreover, differential AT TMOD3 expression is related to changes in AT insulin sensitivity, thereby linking MIH-induced effects on the AT proteome to metabolic changes in overweight/obese humans.