Cognitive fatigue is an important symptom of many brain diseases, including Traumatic Brain Injury (TBI) and Multiple Sclerosis (MS). Cognitive fatigue shares many symptoms with chronic sleep deprivation, best described as cumulative excess wakefulness. If cognitive fatigue is caused by cumulative excess wakefulness, then – if the sleep duration is normal – the function of sleep itself must be impaired. Since sleep aims primarily to replenish the efficiency of cortical inhibitory synapses, it follows that TBI and MS must affect NonREM sleep (light and slow wave sleeps). Strategies providing a more efficient NonREM sleep could demonstrate some therapeutic action against cognitive fatigue.