Eccentric cycling may present an interesting alternative to traditional exercise rehabilitation for patients with advanced COPD, because of the low ventilatory cost associated with lengthening muscle actions. However, due to muscle damage and soreness typically associated with eccentric exercise, there has been reluctance in using this modality in clinical populations. This study assessed the feasibility of applying an eccentric cycling protocol, based on progressive muscle overload, in six severe COPD patients with the aim of minimizing side effects and maximizing compliance. Over 5 weeks, eccentric cycling power was progressively increased in all patients from a minimal 10-Watt workload to a target intensity of 60% peak oxygen consumption (attained in a concentric modality). By 5 weeks, patients were able to cycle on average at a 7-fold higher power output relative to baseline, with heart rate being maintained at ∼85% of peak. All patients complied with the protocol and presented tolerable dyspnea and leg fatigue throughout the study; muscle soreness was minimal and did not compromise increases in power; creatine kinase remained within normal range or was slightly elevated; and most patients showed a breathing reserve > 15 L.min(-1). At the target intensity, ventilation and breathing frequency during eccentric cycling were similar to concentric cycling while power was approximately five times higher (p = 0.02). This study showed that an eccentric cycling protocol based on progressive increases in workload is feasible in severe COPD, with no side effects and high compliance, thus warranting further study into its efficacy as a training intervention.