The purpose of this theoretical study was to estimate the effects of body size and countermeasure (CM) exercise in an all-male crew composed of individuals drawn from a height range representative of current space agency requirements upon total energy expenditure (TEE), oxygen (O 2) consumption, carbon dioxide (CO 2) and metabolic heat (H prod) production, and water requirements for hydration, during space exploration missions. Using a height range of 1.50-to 1.90-m, and assuming geometric similarity across this range, estimates were derived for a four-person male crew (age: 40-years; BMI: 26.5-kg/m 2 ; resting VO 2 and VO 2max : 3.3-and 43.4-mL/kg/min) on 30-to 1,080-d missions, without and with, ISS-like CM exercise (modelled as 2 × 30-min aerobic exercise at 75% VO 2max , 6-d/week). Where spaceflight-specific data/equations were not available, terrestrial data/equations were used. Body size alone increased 24-h TEE (+ 44%), O 2 consumption (+ 60%), CO 2 (+ 60%) and H prod (+ 60%) production, and water requirements (+ 19%). With CM exercise, the increases were + 29 to 32%, + 31%, + 35%, + 42% and + 23 to 33% respectively, across the height range. Compared with a 'small-sized' (1.50-m) crew without CM exercise, a 'large-sized' (1.90-m) crew exercising would require an additional 996-MJ of energy, 52.5 × 10 3-L of O 2 and 183.6-L of water, and produce an additional 44.0 × 10 3-L of CO 2 and 874-MJ of heat each month. This study provides the first insight into the potential implications of body size and the use of ISS-like CM exercise upon the provision of life-support during exploration missions. Whilst closed-loop life-support (O 2 , water and CO 2) systems may be possible, strategies to minimize and meet crew metabolic energy needs, estimated in this study to increase by 996-MJ per month with body size and CM exercise, are required. To sustain humans in space requires the construction of a protective habitat and the generation (and maintenance) of environmental conditions consistent with life. Any habitat, be it a transit vehicle, orbital outpost such as the International Space Station (ISS) in Low Earth Orbit, or future surface habitat, must not only protect crewmembers from the near vacuum of space, but also the extremes of temperature and other space-specific risks including radiation and micrometeorites. Furthermore, appropriate 'life-support' must be provided (i.e. oxygen [O 2 ], water and food), in addition to the management/removal of the by-products of human metabolism (carbon dioxide [CO 2 ], water vapour, metabolic heat, urine, and faeces). On ISS, the provision of life-support is achieved through a combination of supply (and regular re-supply) from the ground (e.g. the Russian 'Progress' expendable cargo and SpaceX's 'Dragon' supply vehicles), and a range of on-board technologies that both manage the internal atmosphere and, increasingly, re-use or recycle by-products (e.g. splitting of CO 2 to generate O 2 and partially [70%] efficient recycling of urine for potable water) 1,2. However, future space...