Fentanyl is an artificial agonist of opioids, and belongs to the μ-opioid receptor agonists. During cardiopulmonary bypass (CPB), a large dose of fentanyl was administered (usually achieved 50–100 μg/kg, loading dose exceeded 50 μg/kg, maintenance dose was 20–30 μg/min). Since the advent of CPB, cerebral complications from overt stroke to subtle cognitive dysfunction after CPB for cardiac surgery have been well documented; the postoperative incidence of dysfunction of cognition exceeded 20–70%. The etiology of these injuries are probably associated with cerebral microemboli, global or regional ischemia, inflammation, cerebral temperature modulation and metabolic abnormality. There are disputes about the effects of large doses of μ-opioid receptor agonist; furthermore, evidence about the effect of large doses of fentanyl on brain injury during CPB have not been reported. Some researchers documented that μ-opioid receptor agonists (including morphine or fentanyl) had neuroprotective effects, and predominantly by the activation of δ1 opioid agonist. While reports that μ-opioid receptor agonists have no neuroprotective effect, even causing brain injury can also been seen.