Multiple sclerosis is known to be associated with both sympathetic and parasympathetic cardiovascular autonomic dysregulation. Thus, patients with multiple sclerosis comorbidity represent a potentially challenging patient population in cardiac surgery, especially in on-pump operations. Despite this, very little is known about the hemodynamics during cardiopulmonary bypass and the optimal perfusion strategy for patients with multiple sclerosis undergoing cardiac operations. In this report, the authors describe a patient with relapsing-remitting multiple sclerosis, who underwent successful triple valve operation for aortic and mitral stenosis and tricuspid valve insufficiency. Distinct blood pressure variations in form of temporary pressure dips were noted during total cardiopulmonary bypass time as well as during the reperfusion period. Pressure variations were not attributable to surgical, pharmacological or perfusion-related manoeuvres. Thus, they most likely represent symptoms of cardiovascular autonomic dysregulation manifesting during cardiopulmonary bypass. In this patient, blood pressure variations terminated spontaneously and remained within an acceptable range without external correction. When treating patients with multiple sclerosis comorbidity, the potential pressure variability due to cardiovascular autonomic dysregulation should be taken into consideration to avoid increased blood pressure volatility due to overcorrection or undercorrection during cardiopulmonary bypass.