Introduction: Physiological de-conditioning associated with spaceflight and disuse environments is a major concern. The Gravity-Loading Countermeasure Skinsuit (GLCS) attempts to recreate gravity via incremental increases in z-axis fibre tension along the body’s longitudinal axis, in a manner analogous to Earth’s gravity. Conceptually, the Mk VI can be utilised by a spaceflight crew during exercise countermeasures and sleep. In order to evaluate whether the GLCS has scope as a countermeasure garment, it was necessary to determine its effect upon the cardiorespiratory responses to maximal aerobic exercise. Methods: In two separate randomised visits, eight male subjects (29.6±5.6 yrs; 177.1±6.8 cm and 74.2±7.1 kg) completed a cycle ergometer maximal oxygen uptake (VO2max) test (Bruce protocol) with stepwise increments of 50W every 3 minutes, whilst wearing either a custom-fabricated Mk VI GLCS or loose fitting clothing (GYM). Cardiorespiratory parameters (breath-by-breath; HR, Vtex, FR, TI/TTOT, VE, RER and VCO2), and subjective comfort, body control and rating of perceived exertion (RPE) were measured continuously and analysed at rest, 75% VO2max and at VO2max. Student’s t-test for paired data and Wilcoxon test was used to analyse physiological (± SEM) and subjective data (±95% confidence intervals). Results: VTex was decreased (p=0.021) in GLCS vs. GYM at 75% VO2max, though no other cardiorespiratory parameter was different between attires at rest, 75% VO2max or VO2max. Absolute VO2max and the wattage required to achieve it were not different between GYM and GLCS (55.35ml/kg/min-1 vs. 54.09ml/kg/min-1 & 275W vs. 268.75W respectively). Furthermore, there was no difference in anaerobic threshold – determined by the elicited VO2 at the point of anaerobic threshold detection – between GYM and GLCS. However, total work product (KiloWatts [KW]) was 12.6% lower in the GLCS (148.1 KW ± 16.9 vs. 132KW ± 15.8 in GYM; p=0.001). Movement discomfort (p=0.02) and body control (p=0.02) – both with scales of 0-10 where 0 is least discomfort and most control – were increased in the GLCS at rest albeit remaining moderate, but were no different at VO2max, whereas RPE and thermal comfort were unaffected throughout. Discussion: The MK VI GLCS did not significantly affect VO2max, maximal wattage or cardiorespiratory responses at VO2max, but did reduce the total work performed. These data suggest that the GLCS does not inhibit oxygen uptake during maximal exercise, but may reduce the duration of work required to achieve a given physiological output. This may have application to as a countermeasure for astronauts and as a rehabilitation tool for a number of populations.