Spinal cord injury (SCI) results in substantial and rapid osteoporosis. Given its rapid onset, assessment of bone changes in the early stages (first 6 months) following SCI is important. This is particularly pertinent if intervention is to be implemented. Quantitative ultrasound (QUS) represents a potential assessment tool for the evaluation of skeletal changes in the early stages following SCI. This longitudinal pilot study assessed changes in QUS measures of calcaneal broadband ultrasound attenuation (BUA) and speed of sound (SOS) in 15 male subjects (age 23.9+/-7.3 years) over a 6-week period. Their mean time since SCI was 110.3+/-34.5 days. Also assessed were bone mineral density of the calcaneus (BMDc) and proximal tibia (BMDt) using dual-energy X-ray absorptiometry (DXA). Confirming the rapid onset of bone loss following SCI, BMDc and BMDt decreased by 7.5+/-3.0% ( p<0.001) and 5.3+/-4.2% ( p<0.001), respectively. QUS was sensitive to these changes. BUA decreased by 8.5+/-6.9% ( p<0.001), whilst SOS decreased by 1.5+/- 1.3% ( p<0.001). Suggesting an influence of the material properties of bone on BUA, BUA was correlated with BMDc at both the initial ( r = 0.68, p<0.01) and final ( r = 0.62, p<0.01) assessments. There were no significant correlations in the magnitude of change over the 6-week assessment period between any of the skeletal measures (all p>0.05). This suggests that skeletal qualities other than material properties also influence QUS measures. Overall, this study confirmed the rapid onset of bone loss following SCI and showed QUS to be a useful portable measure of acute bone changes. This may allow assessment of bone loss and the efficacy of intervention on this loss in the early stages following injury, a period where traditional axial DXA assessment is limited by practical constraints.