Moon and Mars are considered to be future targets for human space explorations. The gravity level on the Moon and Mars amount to 16% and 38%, respectively, of Earth's gravity. Mechanical loading during the anticipated habitual activities in these hypogravity environments will most likely not be sufficient to maintain physiological integrity of astronauts unless additional exercise countermeasures are performed. Current microgravity exercise countermeasures appear to attenuate but not prevent 'space deconditioning'. However, plyometric exercises (hopping and whole body vibration) have shown promise in recent analogue bed rest studies and may be options for space exploration missions where resources will be limited compared to the ISS. This paper therefore tests the hypothesis that plyometric hop exercise in hypogravity can generate sufficient mechanical stimuli to prevent musculoskeletal deconditioning. It has been suggested that hypogravity-induced reductions in peak ground reaction force (peak vertical GRF) can be offset by increases in hopping height. Therefore, this study investigated the effects of simulated hypogravity (0.16G, 0.27G, 0.38G, and 0.7G) upon sub-maximal plyometric hopping on the Verticalised Treadmill Facility, simulating different hypogravity levels. Results show that peak vertical GRF are negatively related to simulated gravity level, but positively to hopping height. Contact times decreased with increasing gravity level but were not influenced through hopping height. In contrast, flight time increased with decreasing gravity levels and increasing hopping height (P < 0.001). The present data suggest that the anticipated hypogravity-related reductions of musculoskeletal forces during normal walking can be compensated by performing hops and therefore support the idea of plyometric hopping as a robust and resourceful exercise countermeasure in hypogravity. As maximal hop height was constrained on the VTF further research is needed to determine whether similar relationships are evident during maximal hops and other forms of jumping.