The extent and characteristics of muscle fatigue of different muscle groups when subjected to a similar fatiguing task may differ. Thirteen healthy young men performed sustained contractions at 50% maximal voluntary contraction (MVC) force until task failure, with four different muscle groups, over two sessions. Per session, one upper limb and one lower limb muscle group were tested (knee extensors and thumb adductor, or plantar and elbow flexors). Changes in voluntary activation level and contractile properties were derived from doublet responses evoked during and after MVCs before and after exercise. Time to task failure differed (P < 0.05) between muscle groups (220 ± 64 s for plantar flexors, 114 ± 27 s for thumb adductor, 77 ± 25 s for knee extensors, and 72 ± 14 s for elbow flexors). MVC force loss immediately after voluntary task failure was similar (-30 ± 11% for plantar flexors, -37 ± 13% for thumb adductor, -34 ± 15% for knee extensors, and -40 ± 12% for elbow flexors, P > 0.05). Voluntary activation was decreased for plantar flexors only (from 95 ± 5% to 82 ± 9%, P < 0.05). Potentiated evoked doublet amplitude was more depressed for upper limb muscles (-59.3 ± 14.7% for elbow flexors and -60.1 ± 24.1% for thumb adductor, P < 0.05) than for knee extensors (-28 ± 15%, P < 0.05); no reduction was found in plantar flexors (-7 ± 12%, P > 0.05). In conclusion, despite different times to task failure when sustaining an isometric contraction at 50% MVC force for as long as possible, diverse muscle groups present similar loss of MVC force after task failure. Thus the extent of muscle fatigue is not affected by time to task failure, whereas this latter determines the etiology of fatigue.