ABSTRACT Objective We evaluated extratemporal metabolic changes with phosphorus magnetic resonance spectroscopy (31P-MRS) in patients with unilateral mesial temporal sclerosis (MTS). Method 31P-MRS of 33 patients with unilateral MTS was compared with 31 controls. The voxels were selected in the anterior, posterior insula-basal ganglia (AIBG, PIBG) and frontal lobes (FL). Relative values of phosphodiesters- PDE, phosphomonoesters-PME, inorganic phosphate - Pi, phosphocreatine- PCr, total adenosine triphosphate [ATPt = γ- + a- + b-ATP] and the ratios PCr/ATPt, PCr/γ-ATP, PCr/Pi and PME/PDE were obtained. Results We found energetic abnormalities in the MTS patients compared to the controls with Pi reduction bilaterally in the AIBG and ipsilaterally in the PIBG and the contralateral FL; there was also decreased PCr/γ-ATP in the ipsilateral AIBG and PIBG. Increased ATPT in the contralateral AIBG and increased γ-ATP in the ipsilateral PIBG were detected. Conclusion Widespread energy dysfunction was detected in patients with unilateral MTS.