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Background People with Parkinson’s disease (PD) are known to have motor learning difficulties. Although numerous studies have demonstrated that a single bout of aerobic exercise (AEX) can facilitate motor learning in non-disabled adults, the same beneficial effect in PD is unknown. Furthermore, associated neuroplastic changes have not been investigated. Objectives This study aimed to determine whether a single bout of aerobic exercise (AEX) can facilitate motor sequence learning in people with PD and to investigate the associated neurophysiological changes. Methods Thirty individuals with PD were recruited and randomized into the exercise group (PD + AEX) and non-exercise group (PD − AEX). At the first visit, corticomotor excitability was assessed using transcranial magnetic stimulation (TMS). All participants then performed a serial reaction time task (SRTT) followed by 20 minutes of moderately-high intensity aerobic exercise (AEX) for the PD + AEX group or rest for the PD − AEX group. The SRTT and TMS were reevaluated at 3 time points: immediately after aerobic exercise (AEX) or rest, on the second day after practice (D2), and a week after practice (D7). Results Both groups showed improvement throughout practice. At retention, the PD + AEX group showed improved SRTT performance on D7 compared to D2 ( P = .001), while the PD − AEX group showed no change in performance. TMS results showed that the PD + AEX group had significantly higher corticomotor excitability than the PD − AEX group on D7. Conclusion A single session of aerobic exercise (AEX) could enhance motor sequence learning and induce neuroplastic changes. Clinicians can consider providing aerobic exercise (AEX) after motor task training for people with PD. Clinical registration: NCT04189887 (ClinicalTrials.gov).