Cold pressure test (CPT) and mental stress test (MST) are distinct tests usually leading to blood pressure (BP) and heart rate (HR) increase. Their patterns in multiple sclerosis (MS) are still unknown. This study assessed cardiovascular reactivity to MST and CPT in patients with MS and controls. MST was performed with Stroop test card. CPT was performed with cold stimulus. The BP and HR were digitally recorded at rest and test phases. The delta (Δ) and the variance of BP and HR were compared between patients and controls. Patients with MS had lower Δ of diastolic BP and HR induced by MST than controls. There were no differences between patients and controls with CPT. The reduced autonomic reactivity to MST but not with CPT suggests that specific central nervous system pathways involved in MST may be responsible for autonomic findings in MS.