Fatigue frequently occurs in myotonic dystrophy type 1 (DM1), but its pathophysiology remains unclear. This study assessed central and peripheral components of exercise-related fatigability in patients with DM1, compared to controls. Methods–Examinations were performed before and after a contraction of the abductor digiti minimi (ADM) muscle sustained for 45 s at 60% of maximal voluntary contraction (MVC). Myoelectric activity was recorded using high spatial resolution surface EMG during twitch stimulations and MVC and was characterized by root mean square, mean power frequency (MPF), and muscle fiber conduction velocity (MFCV). Peripheral nerve excitability was assessed by stimulating the ulnar nerve at the wrist with ADM recordings. Motor cortex excitability testing to transcranial magnetic stimulation included measures of intracortical facilitation and inhibition of motor evoked potentials (MEPs) in ADM muscle. Results–At baseline, patients with DM1 showed altered peripheral nerve and cortical excitability (reduced intracortical facilitation) associated with impaired myoelectric properties. During the fatiguing exercise, the force remained stable, while MPF and MFCV decreased in both DM1 and control groups. After exercise, only refractoriness was reduced in patients with DM1, whereas controls showed marked neuromuscular and cortical changes. Conclusion– Patients with DM1 showed altered excitability of various cortical and neuromuscular components at baseline. However, most of excitability parameters did not vary after exercise in patients with DM1, in contrast to controls. This suggests that excitability properties, frankly altered at baseline, were not prone to be affected further after exercise in patients with DM1.