OBJECTIVE: To investigate whether wearing graduated compression stockings (GCS) could affect the sympatho-adrenergic 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.