Passive limb movement (PLM) has been used as a method of activating the mechanoreflex, inducing limb hyperemia which is nitric oxide (NO) dependent. Breathing hyperoxic gas has been used as a model to elevate free radicals (FR), though it remains to be seen, in humans, if acute elevations in FR alter the mechanoreflex response to PLM, and whether the effect may be sex specific. PURPOSE: The purpose of this study was to compare the male and female central and peripheral hemodynamic responses to dynamic PLM, under normoxic (21% O2) and hyperoxic (100% O2) conditions. METHODS: In 23 young healthy participants (12 female(F) and 11 male(M)) using a single blind design, participants were positioned supine and breathed normoxic (21% O2) and hyperoxic (100% O2) gas from a Douglas bag for 10 minutes, after which 2 minutes of PLM were performed. Central hemodynamic responses (cardiac output [CO], stroke volume [SV], and HR), were measured using a Finometer, while a near-infrared spectrometer (NIRS) was used to assess the microvascular response (tissue oxygen saturation, StO2%) at baseline and during the PLM. RESULTS: No sex differences in hemodynamics were observed at baseline in normoxia (p>0.05). In response to PLM, both sexes increased HR and CO from baseline (p<0.05); however, males elicited significantly higher CO response than females (ΔCO: 1.7±0.7 vs. 0.9±0.6 L/min, p<0.05). Peripherally, PLM increased StO2 from baseline for both sexes (p<0.05), though there was a significant difference in the peripheral response to PLM between the sexes (M: 4.2±2.0 vs F: 2.3±2.7 ΔStO2%, p<0.05). Hyperoxia had no effect on baseline CO or StO2 (p>0.05) or the response to PLM, and the sex difference persisted (ΔCO: 1.8 ± 1.0 vs 1.1 ± 0.6 L/min, M v. F) (p<0.05). PLM induced significant changes in StO2, which were not different from normoxia, though the sex specificity persisted (M: 4.5±1.8 vs F: 2.1±2.7 ΔStO2%, p<0.05). CONCLUSION: The present study provides further evidence that females exhibit an attenuated mechanoreflex as compared to males, which may reduce CVD risk. Though, unlike the macrovascular responses to PLM which have been reported to be similar between sexes, the microvascular responses to PLM may differ. In the current model, prior inhalation of 100% oxygen had no effect on the mechanoreflex in in young healthy males and females.