Beat-to-beat fluctuations in heart rate are partially controlled by the autonomic nervous system and may be altered by a spinal cord injury. The purpose of the present investigation was to examine the role of the autonomic nervous system in modulating the heart rate response to head-up tilt (HUT) in subjects with low lesion paraplegia. Nineteen subjects with paraplegia and nine age-, height-, and weight-matched control subjects consented to participate. A three lead ECG was used to acquire heart rate (HR), cardiac sympathetic [low frequency component of R-R interval variability (LFRRI)], vagal [high frequency component of R-R interval variability (HFRRI)] and sympatho-vagal balance (LF/HF). A finger photoplethysmograph was used to assess beat-to-beat blood pressure for the estimation of sympathetic vasomotor tone [low frequency component of peak systolic blood pressure variability (LFSBP)]. The results showed a significant main effect for tilt angle for the HR response to HUT, which was comparable between the groups. LFRRI was significantly increased (P < 0.001) and HFRRI was significantly reduced (P < 0.001) across tilt angle in the control group, whereas subjects with paraplegia demonstrated no significant change in LFRRI, but significantly reduced HFRRI (P < 0.001) across tilt angle. There was a significant interaction effect for LF/HF (P < 0.05). LFSBP was significantly reduced in the group with paraplegia compared to controls (P < 0.05). These findings suggest that although cardiac autonomic control is intact, there is a blunted sympathetic response to HUT in subjects with low lesion paraplegia, which may implicate an altered baroreceptor response to acute orthostatic provocation.