Deep Space exploration is on the horizon. Our understanding of plant responses to space environments will provide the foundation for growing plants in Low Earth Orbit, the Moon, Mars and beyond. C4 plants like maize and sorghum have a more efficient photosynthesis than C3 plants such as wheat and rice due to a CO2-concentrating mechanism (CCM). How this CCM and the performance of C4 plants are impacted by space travel is unknown. We aim to compare the impact of space-station conditions on C3 and C4 metabolism using Brachypodium and Setaria as model systems for C3 and C4 plants, respectively. Our discoveries will provide fundamental knowledge about C3 and C4 metabolism in space and could also be leveraged for evaluating the potential for growing small-stature cereal and vegetable C4 crops for bio generative support in future space explorations.