Objective: Individuals with spinal cord injury (SCI) often present signs and symptoms of median nerve (MN) pathology. Preclinical signs identification of MN pathology might facilitate early intervention to prevent or delay carpal tunnel syndrome in SCI. We assessed if ultrasound parameters changed in response to upper extremity (UE) circuit training exercise in individuals with paraplegia and able-bodied individuals. Design: Case-control study. Participants: Adults (N=32) with paraplegia (n=16) and age- and sex-matched able-bodied controls (n=16). Intervention: Circuit training exercise. Main Outcome Measures: MN ultrasound evaluation at the pisiform and radius before and after UE exercise. Ultrasound parameters included cross-sectional area (CSA), and gray scale (GS). Data presented as mean ± SD. Results: Pre-exercise CSAs were larger in SCI at the radius (12.0±2.9 vs 9.0±2.1; P=.003), but not the pisiform (9.8±3.1 vs 9.1±1.7; P=.431). There were no statistical differences in MN response to exercise between groups (all P≥.293). Across participants, CSA changes were inversely associated with their pre-exercise values at the pisiform (r=–0.648; P<.001) and the radius (r=–0.366; P=.043). Participants with pre-exercise CSA values ≥10.00 mm2 at the pisiform responded to exercise with decreases in CSA (mean change ± SD, –2.0±1.5; P=.002) and GS (–2.8±6.2; P=.029). Participants with pre-exercise CSA ≤9.99 mm2 at the pisiform responded to exercise with no change in CSA (mean change ± SD, 0.7±2.5; P=.002) and increased GS (3.2±7.2; P=.029). Conclusions: CSA exercise response was more strongly related to pre-exercise MN values than presence or absence of SCI.