To further understand the mechanisms of perturbations in bone remodeling following severe burn injury, the biomechanical properties, genetic expression, and serological markers were evaluated in rodents at six time intervals within 6 weeks following injury. Moreover, these effects were observed in rodent tibia and lumbar vertebrae to explore possible skeletal site localization of this pathologic bone loss. Rodents underwent either thermal injury (100°C water, 30 seconds, 30% BSA) or sham burn. Bone mineral density was evaluated though peripheral quantitative computer tomography, and specialized apparatus measured the weight bearing capacity of tibia and lumbar vertebrae. Markers of bone resorption (RANK ligand, osteocalcin) and bone formation (osteoprotegerin, procollagenase type 1 alpha 2) were measured at 7, 14, and 21 days following injury, and serum RANK-ligand levels were observed at these time intervals. Rodent body mass, bone mineral density, and weight bearing capacity were negatively influenced both acutely and several weeks following burn injury. Moreover, a genetic expression profile favoring increased bone resorption and lower bone formation was demonstrated. Our serum analysis findings of significantly increased RANKL 1 and 2 weeks following injury support the increased expression of bone resorption markers. Furthermore, these effects occurred sooner and were more pronounced in the rodent lumbar vertebrae than tibia. These results suggest that severe burn injury results in perturbations in bone remodeling secondary to increased bone resorption and diminished bone formation, impacting both bone mineral density and weight bearing capacity. Furthermore, these processes had a skeletal site effect more pronounced in the lumbar vertebrae. With a better understanding of the mechanisms of burn-injury bone loss, targeted therapies can be implemented to improve long-term clinical outcomes.