Restless legs syndrome (RLS) was very common among ESRD patients. However, the physiopathologic mechanisms of RLS in ESRD patients were largely unclear. Here we analyzed the thalamic metabolites using 1H MRS and the correlation between sleep/RLS score and metabolites, compared with corresponding normal controls. The results showed that the Cho/Cr ratio increased and NAA/Cr ratio decreased in thalamus of ESRD patients. The correlation between Cho/Cr ratio and RLS score was significant. It indicated that the sleep disturbance in ESRD patients with RLS might be associated with the abnormal thalamocortical activation of human sleep regulation system.