It is essential to take a rest adequately to avoid accumulation of fatigue and disruption of homeostasis. However, the neural mechanisms of the decision making based on the level of fatigue, whether to take a rest or not, are not well understood. In the present study, we aimed to clarify the neural substrates of the decision making based on the (subjective) level of fatigue and used magnetoencephalography to assess the neural activities. Fifteen healthy volunteers participated in this study, which was approved by the Ethics Committee of Osaka City University, and gave written informed consent for participation. This study consisted of decision and control experiments performed in a cross-over fashion. In the decision experiment, the participants performed reverse Stroop test trials and were intermittently asked to decide whether to take a rest or continue. In the control experiments, the participants were instructed to press a response button without making any decisions. Changes in the oscillatory brain activities caused by making decisions were assessed using a narrow-band adaptive spatial filtering method. In relation to making decisions to take a rest, decreased theta (4-8 Hz) band power in the left Brodmann's area (BA) 31, decreased alpha (8-13 Hz) band power in the left BA 10 and left BA 9, and decreased beta (13-25 Hz) band power in the right BA 46 and left BA 10 were observed as compared with those in the control trials. The decreased theta band power in the BA 31 was positively correlated with the subjective level of fatigue just after the decision experiment. We demonstrated that, in addition to the dorsolateral prefrontal cortex and frontal pole, the posterior cingulate cortex plays an important role in the decision making based on the level of fatigue. Our findings may help clarify the neural substrates of the decision making related to fatigue and may help understanding the pathophysiology of fatigue and fatigue related problems.