We evaluated spectroscopy findings at the deep white matter in Machado-Joseph disease (MJD). We obtained brain MRI and single-voxel proton MR spectroscopy (MRS) over the superior-posterior region of the left hemisphere at the level of the corpus callosum in 40 patients (44.6 ± 2.3 years-old) and 27 controls (31.4 ± 3.6 years). Four patients were excluded due to poor quality spectra. We observed a decrease in signal intensity of N-acetylaspartate relative to creatine-phosphocreatine signal (NAA/Cr) in MJD compared to control [1.63 ± 0.41 (1.15-2.76) versus 1.97 ± .51 (1.50-2.92); U test = 219.0; P < .001]. No statistical difference was observed in choline-containing compounds relative to creatine (Cho/Cr). There was no significant correlation between NAA/Cr and clinical and genetic variables. Due to the younger age of the control group, we performed a secondary analysis in a subgroup of 15 MJD patients matched by age to 15 controls. Matching was performed blindly to MRS results and subject identification, except for age and sex. A statistically significant difference was observed in NAA/Cr ratios (U test = 44.0; P= .004), as well as Cho/Cr levels (U test = 53.0; P= .014). We conclude that the metabolic abnormalities observed in the deep white matter in MJD suggest extensive neuronal and axonal dysfunction in these patients.