Purpose: To assess the spatial extent of the decrease in the neuronal marker N-acetyl-aspartate (NAA) relative to creatine (Cr) in patients with localization-related epilepsy, and to assess clinical differences between patients with and without widespread NAA/Cr reduction. Methods: We studied 51 patients with localization-related epilepsy. Patients were divided into three groups according to the EEG investigation: (a) temporal lobe epilepsy (TLE, n = 21), (b) extratemporal lobe epilepsy (extra-TLE, n = 20), and (c) multilobar epilepsy (patients with a wider epileptogenic zone, n = 10). We acquired proton magnetic resonance (MR) spectrocopic imaging (H-1-MRSI) of temporal and frontocentroparietal regions in separate examinations for both patients and controls. NAA/Cr values 2 standard deviations below the mean of normal controls were considered abnormal. Results: Twenty-three (45%) patients including 12 with TLE had normal MR imaging including volumetric studies of the hippocampus. Forty-nine (96%) patients had low NAA/Cr, indicating neuronal dysfunction in either temporal and/or extratemporal H-1-MRSIs; 38% of patients with TLE and 50% of patients with extra-TLE also had NAA/Cr reduction outside the clinical and EEG-defined primary epileptogenic area. The NAA/Cr reduction was more often widespread in the multilobar group [six (60%) of 10] than in temporal or extratemporal groups [five (31%) of 16]. Nonparametric tests of (a) seizure duration, (b) seizure frequency, and (c) lifetime estimated seizures showed no statistically significant difference (p > 0.05) for TLE and extra-TLE patients with or without NAA/Cr reduction outside the seizure focus. Conclusions: Of patients with localization-related epilepsy, 40-50% have neuronal metabolic dysfunction that extends beyond the epileptogenic zone defined by clinical-EEG and/or the structural abnormality defined by MRI.