The neural substrates related to periodic leg movements during sleep (PLMS) remain uncertain, and the specific brain regions involved in PLMS have not been evaluated. We investigated the brain regions associated with PLMS and their severity using the electroencephalographic (EEG) source localization method. Polysomnographic data, including electromyographic, electrocardiographic, and 19-channel EEG signals, of 15 patients with restless legs syndrome were analyzed. We first identified the source locations of delta-band (2-4 Hz) spectral power prior to the onset of PLMS using a standardized low-resolution brain electromagnetic tomography method. Next, correlation analysis was conducted between current densities and PLMS index. Delta power initially and most prominently increased before leg movement (LM) onset in the PLMS series. Sources of delta power at -4~-3 seconds were located in the right pericentral, bilateral dorsolateral prefrontal, and cingulate regions. PLMS index was correlated with current densities at the right inferior parietal, temporoparietal junction, and middle frontal regions. In conclusion, our results suggest that the brain regions activated before periodic LM onset or associated with their severity are the large-scale motor network and provide insight into the cortical contribution of PLMS pathomechanism.