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We utilized a porcine cardiac arrest model to compare early sequential hypothermia (ESH) with delayed hypothermia (DH) and no hypothermia (NH) to investigate the different effects on cerebral function after resuscitation.After return of spontaneous circulation (ROSC), resuscitated 24 pigs divided into three groups. The ESH group implemented early sequential hypothermia immediately, and the DH group implemented delayed hypothermia at 1 h after ROSC. The core temperature, hemodynamic parameters and oxygen metabolism were recorded. Cerebral metabolism variables and neurotransmitter in the extracellular fluid were collected through the microdialysis tubes. The bloods were analyzed for venous jugular bulb oxygen saturation, lactate and neuron specific nolase. The cerebral function was evaluated using the cerebral performance category and neurologic deficit score at 72 h after ROSC and cerebral histology in the right posterior frontal lobe were collected.ESH reached the target temperature earlier and showed more favorable outcomes of neurological function than DH. Specifically, early sequential hypothermia reduced cerebral oxygen and energy consumption and decreased extracellular accumulation of neurotransmitters after resuscitation and protected the integrity of the BBB during reperfusion.Early sequential hypothermia could increase the protection of neurological function after resuscitation and produce better neurological outcomes.The institutional protocol number: 2010-D-013.