Neuromuscular fatigue is widely accepted as a phenomenon which affects exercise tolerance and represents not only a limiting factor during sporting competitions, but can also influence the quality of life for the elderly and patients with neurological diseases by restricting mobility. Understanding the underlying mechanism(s) of neuromuscular fatigue is essential to influence the limits of exercise tolerance. Previous research suggested numerous mechanisms inducing neuromuscular fatigue that were differentiated depending on their peripheral or central origin (Gandevia, 2001). The relation between exercise intensity and duration has been described as the most crucial factor determining exercise tolerance (Walsh, 2000), likely due to the specific physiological responses and energy demands associated with each intensity domain. Evidence suggests indeed that the contribution of central and peripheral processes is dependent on exercise intensity and duration (Thomas et al, 2015). Neuromuscular fatigue seems to be predominantly of peripheral origin during high-intensity exercise (Burnley et al, 2012). This thesis aims to enhance our understanding of the mechanisms underlying neuromuscular fatigue during high-intensity exercise, which may provide essential practical implications for a wide range of athletic events and a variety of areas within the health sector.