Purpose: Vagus nerve stimulation (VNS) has been successfully applied to reduce seizure frequency in numerous patients with epilepsy. However, various side effects, including dyspnea and bradycardia have been reported, that appear exercise related in some patients. This pilot study aims to obtain insight in the cardiorespiratory effects of VNS during both rest and exercise. Methods: Patients with a VNS device who experience side effects during exercise are compared with patients without side effects. Respiratory and cardiac parameters measured during rest and exercise include heart rate, breathing frequency and tidal volume. Results: Sixty-two episodes of VNS in five patients with and five patients without side effects were recorded. In addition, five control subjects have been measured. During rest, all subjects showed stable values for the cardiorespiratory parameters. During the first minutes of exercise, heart rate, breathing frequency and tidal volume increased. Thereafter, a steady state was reached again for all subjects. During VNS episodes, eight out of 10 patients showed a small but consistent decrease in heart rate, along with an increase in breathing frequency in eight out of nine patients. Tidal volumes decreased during VNS episodes. These effects, induced by VNS, occurred during both rest and exercise. Magnitude of these effects varied between patients, but was not necessarily related to the intensity of the experienced side effects. Conclusion: This pilot study shows that VNS causes an increase in breathing frequency and a decrease in tidal volume and heart rate in the majority of patients, during both rest and exercise.