Changes in near-infrared spectroscopy-derived regional tissue oxygen saturation (StO2) during a vascular occlusion test (VOT; ischemic provocation of microcirculation by rapid inflation and deflation of a tourniquet) allow estimating peripheral tissue O2 consumption (desaturation slope; DS), vascular reactivity (recovery slope; RS) and post-ischemic hyperperfusion (AUC-H). The effects of isolated alterations in the inspiratory fraction of O2 (FiO2) and changes in expiratory CO2 remain to be elucidated. Therefore, in this secondary analysis we determined the effects of standardized isolated instances of hypoxia, hyperoxia, hypocapnia and hypercapnia on the VOT-induced StO2 changes in healthy volunteers (n=20) to establish reference values for future physiological studies. StO2 was measured on the thenar muscle. Multiple VOTs were performed in a standardized manner: i.e. at room air (baseline), during hyperoxia (FiO2 1.0), mild hypoxia (FiO2≈0.11), and after a second baseline, during hypocapnia (end-tidal CO2 (etCO2) 2.5-3.0vol%) and hypercapnia (etCO2 7.0-7.5vol%) at room air. Differences in DS, RS, and AUC-H were tested using repeated-measures ANOVA. DS and RS remained constant during all applied conditions. AUC-H after hypoxia was smaller compared to hyperoxia (963%*sec vs hyperoxia 1702%*sec, P=0.005), while there was no difference in AUC-H duration between hypoxia and baseline. The StO2 peak (after tourniquet deflation) during hypoxia was lower compared to baseline and hyperoxia (92% vs 94% and 98%, P<0.001). We conclude that in healthy volunteers at rest, common situations observed during anesthesia and intensive care such as exposure to hypoxia, hyperoxia, hypocapnia, or hypercapnia, did not affect peripheral tissue O2 consumption and vascular reactivity as assessed by VOT-induced changes in StO2. These observations may serve as reference values for future physiological studies. This study represents a secondary analysis of an original study which has been registered at ClinicalTrials.gov nr: NCT02561052.