Abstract Purpose This study was to compare the upper extremity muscular function and cross-sectional area (CSA) between wheelchair users and a pedestrian group and to observe how the changes in the muscle CSA affected upper extremity muscle function. Methods The study was conducted on 10 patients with spinal cord injury (SCI) who were divided into two groups based on whether they used wheelchairs (wheelchair using [WU] group and pedestrian [PS] group). The Mann-Whitney U-test was used to analyze the data and determine whether there were significant differences between the groups. Results Muscle mass in the WU group was significantly lower than in the PS groups (p<0.01), while body fat percentage in the WU group was significantly higher than in the PS group (p<0.05). The peak torque of shoulder external and right internal rotation was higher in the WU group than in the PS group (p<0.05). Wrist muscle function was not significantly different for either group. In addition, the CSA of the right wrist extensor carpi radialis longus and left extensor digitorum communis was higher in the WU group than in the PS group (p<0.05). Conclusion Using a manual wheelchair may benefit upper extremity function by increasing CSA and muscle function in patients with SCI despite having a negative effect on body composition. However, there is an increased risk of injury with SCI associated with upper extremity overload; thus, an effective exercise protocol is needed to prevent muscle imbalance and injury.