Potential causes of general fatigue include chronic pain, respiratory compromise, depression, "type A" behavior, sleep disorders, and dysfunction of the reticular activating system -- a component of the central nervous system that controls the overall level of activity, including wakefulness, attentiveness, and sleep.

Proposed causes for muscular fatigue in PPS include overuse myopathy, muscle fiber type disproportion, defective muscular function, and neuromuscular junction transmission defects.