The muscle metaboreflex activation has been shown essential to reach normal hemodynamic response during exercise. It has been demonstrated that patients with multiple sclerosis (MS) have impaired autonomic functions and cardiovascular regulation during exercise. However, to the best of our knowledge, no previous research to date has studied the metaboreflex in MS patients. The purpose of this study was to investigate the hemodynamic response to metaboreflex activation in patients with MS (n = 43) compared to an age-matched, control group (CTL, n = 21).Cardiovascular response during the metaboreflex was evaluated using the post-exercise muscle ischemia (PEMI) method and during a control exercise recovery (CER) test. The difference in hemodynamics between the PEMI and the CER test was calculated and this procedure allowed for the assessment of the metaboreflex response. Hemodynamics was estimated by impedance cardiography.The MS group showed a normal mean blood pressure (MBP) response as compared to the CTL group (+6.5 ± 6.9 vs. +8 ± 6.8 mmHg, respectively), but this response was achieved with an increase in systemic vascular resistance, that was higher in the MS with respect to the CTL group (+137.6 ± 300.5 vs. -14.3 ± 240 dyne · s(-1) cm(-5), respectively). This was the main consequence of the MS group's incapacity to raise the stroke volume (-0.65 ± 10.6 vs. +6.2 ± 12.8 ml, respectively).It was concluded that MS patients have an impaired capacity to increase stroke volume (SV) in response to low level metaboreflex, even if they could sustain the MBP response by vasoconstriction. This was probably a consequence of their chronic physical de-conditioning.