Objective To observe changes in the working memory and brain functional imaging on functional magnetic resonance imaging(fMRI) after 36 hours sleep deprivation (SD) in healthy volunteers and to explore the possible mechanism of the changes.Methods FMRI scannings were performed in ten male healthy young volunteers before and after 36 hours SD and results were analyzed using SPM2 software.Subjects were also tested LTR and PLUS task to measure the persistence and operation of working memory before and after 36 hours SD.Results The reaction time of LTR task after 36 hours SD ( (866 ± 102) ms)was significantly longer than that before SD ( (754 ± 91 ) ms, t = 2.59, P < 0.01 ).The reaction time of PLUS task after SD ( (848 ± 94) ms) was significantly longer ( t = 2.37, P < 0.05 ) than that before SD ( (756 ± 79) ms).The error rate of LTR task after SD (95.3% ± 3.56% ) was significantly higher (t=3.52,P < 0.01 ) than that before SD (84.8% ± 8.71% ).The error rate of PLUS task after SD (95.7% ±4.72% ) was significantly higher (t =3.38 ,P <0.01 ) than that before SD (84.2% ±9.66% ).There were no significant differences between the two tasks.The frontal and parietal lobes, anterior cingulate gyrus and thalamus were activated during memory tasks testing before SD.Brain activation was broader and stronger in PLUS task than in LTR task.After SD, activation in parietal lobe was decreased and activation in prefrontal and thalamus was increased significantly.Conclusions The working memory performance decreased after SD.Both LTR and PLUS tasks of working memory activate frontal and parietal lobes, anterior cingulate gyrus and thalamus.The activation of parietal lobe decreased and the activation of prefrontal lobe and thalamus increased after 36 hours SD.This is the possible mechanism of SD to causes the cognition decline.