Purpose <p>The aim of this work is to determine the relationship between the cross-sectional area (CSA) of the vagus nerve and cardiovagal function in people with multiple sclerosis (pwMS) and healthy controls (HC).</p> Methods <p>We enrolled 50 pwMS and 50 HC. All participants underwent an ultrasound of the vagus nerve and autonomic nervous system testing. The Croatian version of the COMPASS-31 questionnaire was used as a measure of autonomic symptom burden. Cardiovagal function was evaluated with the respiratory sinus arrhythmia (RSA), Valsalva ratio (VR), and heart rate variability.</p> Results <p>The mean vagus CSA in pwMS was 2.03 ± 0.49 mm² on the right side and 1.72 ± 0.38 mm² on the left side. The mean vagus CSA in HC was 2.08 ± 0.50 mm² on the right side and 1.74 ± 0.37 mm² on the left side. There was no statistically significant difference between the two groups in right (<i>p</i> = 0.615) or left (<i>p</i> = 0.866) vagus CSA. In the HC, there was a statistically significant positive correlation between the mean right CSA and both RSA (<i>r</i>_p = 0.331, <i>p</i> = 0.019) and VR (<i>r</i>_p = 0.327, <i>p</i> = 0.020). On univariable linear regression analysis in the HC group, the mean right CSA was a predictor of both RSA (<i>B</i> = 5.599, 95% CI 0.974–10.224, <i>p</i> = 0.019) and VR (<i>B</i> = 0.253, 95% CI 0.041–0.466, <i>p</i> = 0.020). These findings were not present in pwMS.</p> Conclusions <p>The loss of correlation between vagus nerve CSA and parameters of parasympathetic nervous system function in pwMS corroborates the presence of cardiovagal dysfunction in multiple sclerosis.</p>