Background: Late infantile metachromatic leukodystrophy (MLD) is an autosomal recessive lysosomal storage disorder that causes severe demyelination of the nervous system. The neuronal metabolite N-acetylaspartate (NAA) serves as a source of acetyl groups for myelin lipid synthesis in oligodendrocytes and is known as a marker for neuronal and axonal loss. NAA and other metabolite levels measured by proton magnetic resonance spectroscopy (MRS) correlate with performance of the brain in normal children. There is a need for sensitive measures of disease progression in patients with MLD to enable development of future reatments. Methods: A cross-section of 13 children with late infantile MLD were examined by proton MRS. Signals from NAA, total choline, and total creatine in the deep white matter were measured and correlated with the results of cognitive and motor function tests. Results: The NAA signal decreased as the disease process advanced. Motor function, measured by the Gross Motor Function Measure–88, varied from 13 (only head movement in the supine position) to 180 (able to walk) across the study cohort, demonstrating a wide range in functional status. Similarly, varied decreases were observed in cognitive function. We report strong positive correlations between standardized measures of motor and cognitive function and NAA levels in the deep white matter. Conclusions: We suggest that NAA levels could serve as a sensitive biomarker in children with MLD. Proton MRS may provide a valuable tool for measuring the effects of treatment interventions in this disorder.