Objective: To investigate whether wearing graduated compression stockings (GCS) could affect the sympathoadrenergic and heart rate variability (HRV) responses at rest and after a strenuous wheelchair exercise in individuals with spinal cord injury (SCI). Design: Crossover trial. Setting: Department of Physical Medicine and Rehabilitation, Saint Etienne, France. Participants: Nine men with SCI (five with low paraplegia: LP, four with high paraplegia: HP). Interventions: Two maximal wheelchair exercise tests: with and without GCS (21 mmHg). Main outcome measures: HRV measurements: high frequency (HF), low frequency (LF), and LF/HF ratio. Norepinephrine (NOR) and epinephrine (EPI), at rest and post-exercise. Secondary measures were: blood pressure, heart rate, maximal power output, oxygen uptake, stroke volume, cardiac output, at rest, during and after exercise. Results: When wearing GCS: LFnu wavelet-post significantly increased and HFnu wavelet-post significantly decreased (P < 0.05) in SCI subjects, leading to an enhance ratio of LF wavelet /HF wavelet and a significantly increased in NOR rest (P < 0.05). Conclusions: GCS induces an enhanced sympathetic activity in individuals with paraplegia, regardless of the level of the injury. Enhanced post-exercise sympathetic activity with GCS may help prevent orthostatic hypotension or post-exercise hypotension.