Fatigue is defined as "the decline in muscular tension capacity with repeated stimulation".
Motor unit fatigue is the result of many factors. Different types of exercise and intensities can produce fatigue in different sites:

Neural Fatigue

This is failure (voluntary or involuntary) of the nerve impulse, resulting in the reduction of active motor units or frequency of motor unit firing, possibly due to:

• Nerve cells in motor cortex of brain send weaker impulses to muscles for voluntary contractions.
• Synapses between nerve fibres in pathway from brain (motor cortex) to final motor nerve of spinal cord, just before peripheral nervous system.
• Neuromuscular junction fatigue, where the impulse (action potential) fails to cross from the motor nerve to the muscle fibre (motor endplate). Evidence suggests that there is decreased Acetylecholine (Acl) - the transmitter substance.

Evidence suggests that fatigue is more likely to occur in the muscle before the motor nerve.

Muscular Fatigue

This is failure of the muscle to continue to generate force, due to:

• A significant reduction in the glycogen fuel content of the active muscle fibres is related to fatigue during prolonged submaximal (endurance) exercise. This "nutrient" fatigue occurs even though sufficient oxygen is available for aerobic energy production.
• Lack of oxygen (Short term, maximal exercises) results in an increased level of lactic acid. The lactate inhibits the coupling of the myosin crossbridges on the actin. The lactic acid also reduces the effectiveness of muscle cell enzymes. A lack of oxygen also results in rapid depletion of ATP and PC.
• Dehydration often results in losses of sodium and potassium in the sweat. These losses effect the transmission of the impulse across the sarolemma (surface) of the muscle.
• Occlusion (cutting off) of the blood supply due to contraction of large muscle mass resulting in high muscle pressure on blood vessels.