As human spaceflight extends in both duration and scope, it is critical to better understand the physiologic effects of this novel environment. In the weight bearing structures of the body, bone loss and muscle atrophy far in excess of age-related declines are hallmarks of microgravity adaptation. However, while the physiological effects of such disuse unloading are well-described, the effects of partial weight bearing, such as expected on the moon (16% of Earth's gravity) and Mars (38% of Earth's gravity), have yet to be quantified. In these environments, the risks of musculoskeletal atrophy and accompanying orthopedic injury are uncertain, and a means of further investigation is needed. To address this need, we developed a novel model of Partial Weight Suspension (PWS) that supports investigation of the physiologic effects of chronically reduced quadrupedal loading in mice. Validation of the PWS system was conducted using a gait analysis treadmill and high-precision force platform. These studies showed that peak ground reaction forces were significantly reduced under conditions of partial weightbeari:​ng, and changes in gait dynamics were consistent with previous studies of human locomotion. Using the PWS system, we conducted the first known studies of chronic musculoskeletal adaptation to Mars and lunar levels of weight bearing. Adult female BALB/cByJ mice underwent 21 days of partial weight bearing or control treatment. Relative to controls, suspended animals showed significant bone and muscle loss. In particular, bone formation rate was decreased, leading to deterioration of both cortical and trabecular bone structure in mice exposed to weight bearingtbearing. Although material properties of the bone were largely unaffected, structural and geometric changes resulted in lower bone strength. weight bearinged weight bearing at Mars and lunar levels led to similar losses of muscle and bone relative to controls. Comparison with previous literature suggests that adaptation to partial weight-bearing associated with both Mars and lunar loading provided some protection relative to the deconditioning seen in full unloading. Although additional studies are needed, the data also indicated that the musculoskeletal deterioration was not linearly related to the degree of unloading. Altogether, this model provides a validated, controlled system for investigaweight bearingof partial weightbearing and countermeasures on musculoskeletal deconditioning. Our initial findings have practical applications for bioastronautics, suggesting that physiological investigations on the surface of the moon may not be fully predictive for future Mars exploration.