Purpose To investigate the difference of cerebral blood flow between sleep deprivation and rest wakefulness.Materials and Methods Fifty subjects were recruited from universities in Xi'an from October 2020 to December 2021.The psychomotor vigilance test(PVT)task was used to measure sustained attention.Arterial spin labeling technique was used to analyze and compare the relative cerebral blood flow(rCBF)between sleep deprivation and rest wakefulness.The correlation between altered rCBF of specific brain regions and PVT task performance after sleep deprivation was analyzed.Results Compared with rest wakefulness,rCBF in bilateral dorsolateral prefrontal lobe,bilateral parietal lobule,left orbital middle frontal gyrus,bilateral middle temporal gyrus,right posterior central gyrus,and bilateral angular gyrus was significantly decreased after sleep deprivation.The rCBF of bilateral thalamus,left precuneus,right medial prefrontal lobe,left posterior cingulate gyrus,and left inferior temporal gyrus was significantly increased(FDR corrected,P<0.05,cluster size≥20 voxels).The changes of rCBF in left dorsolateral prefrontal lobe and right parietal lobule were significantly negatively correlated with the PVT task performance(r=-0.56,P<0.001;r=-0.64,P<0.001),and the change of rCBF of left precuneus was significantly positively correlated with the PVT task performance(r=0.72,P<0.001).Conclusion The abnormal changes of CBF in default mode network,frontoparietal network-related brain regions and thalamic may be the important neural mechanism of sustained attentional decline after sleep deprivation.