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Exercise induced performance fatigue has been shown to impair many aspects of fine motor function in the distal upper limb. However, most fatiguing protocols do not reflect the conditions experienced with computer use. The purpose of this study was to determine how a prolonged, low-force mouse clicking fatigue protocol impacts performance fatigue of the distal upper limb for gamers and non-gamers. Participants completed a total of 1 h of mouse clicking at 5 clicks per second. Muscle fatigue and performance were intermittently assessed. RMS amplitude increased for the forearm flexors throughout the fatigue protocol. Accuracy decreased following the first bout of clicking and returned to baseline values after 40-min. EDC and ECU displayed the greatest muscle activity while aiming, producing 11.4% and 12.9% of MVC, respectively. These findings indicate that mouse clicking may not result in performance fatigue, however, high levels of extensor activity may explain common injuries among gamers. [ABSTRACT FROM AUTHOR]