Oxygen is an important modulator of vascular function, but its influence on the veins is incompletely understood. While age‐related impairments on arterial function have been well‐established, the effects of ageing on the venous circulation have not been examined. The purpose of this study was to determine the effects of hypoxia and hyperoxia on lower limb venous function in healthy young and older humans. We tested the hypothesis that the venomotor response to hypoxia and hyperoxia is attenuated with ageing.In fifteen young (29±8 years, mean±SD) and seven older (age: 66±6 years) healthy individuals, we assessed peripheral oxygen saturation (SpO2) and the cross‐sectional area (CSA) of the great saphenous vein (GSV; Doppler ultrasound) during a standard thigh cuff inflation‐deflation protocol (11 min) while breathing room air, hypoxia (fraction in inspired oxygen [FIO2]: 0.10) or hyperoxia (FIO2: 0.50), in a single‐blinded, randomized manner. The pressure‐CSA relationship was modelled using an established quadratic regression equation and GSV compliance derived.Resting SpO2 was decreased by hypoxia (80.9±5.6%) and increased by hyperoxia (98.8±0.7%) compared to room air (96.3±1.1%, p<0.001) in both young and older groups. In the young group, hypoxia selectively decreased GSV CSA (index of capacity) (13.4±5.7 mm2, p<0.001) compared to room air (17.0±7.9 mm2), while GSV compliance was unchanged (p=1.000). In contrast, hyperoxia did not alter GSV CSA (17.1±8.7 mm2, p=0.883) in the young group, but GSV compliance was increased by 2‐3 fold compared to room air and hypoxia (p=0.007). In room air, GSV capacity was almost double in older participants (+19.6m2, p=0.016), but GSV compliance was not different from the younger group (p=0.423). Neither hypoxia nor hyperoxia affected GSV CSA and compliance in the older group (p>0.05 vs. room air).These preliminary data suggest that in young healthy individuals, hypoxia reduces GSV capacity and hyperoxia increases GSV compliance. However, such manipulations in blood oxygenation do not alter venous function in older healthy individuals. Further investigations are required to determine whether local and/or chemoreflex‐mediated sympathetic mechanisms underpin such alterations in venous function.