In contrast to earlier observations, recent studies have demonstrated that supratentorial lacunar infarcts in the white matter may cause mild neuropsychological impairments. The origin of these cognitive disturbances is yet unknown. In the current study proton magnetic resonance spectroscopy (1H MRS) was used to elucidate the hypothesized relation between a lacunar infarct, metabolic alterations, and neuropsychological function. Patients with a single supratentorial lacunar infarct (n = 26) were compared with patients with a mild myocardial infarct (n = 12) and healthy controls (n = 12) on a comprehensive neuropsychological examination, and on the N-acetyl-aspartate/creatine, choline/creatine and lactate/creatine ratios. The volume of interest of the MRI/MRS examination was located in normal-appearing white matter of the centrum semiovale at a distance from the infarct, in both the ipsilateral and contralateral hemisphere. On neuropsychological examination patients with a lacunar infarct performed worse than both patients with a myocardial infarct and healthy controls. The N-acetyl-aspartate/creatine ratio was decreased in patients with a lacunar infarct compared with the other two groups. More important, this decrease in neurometabolites was significantly correlated to the level of cognitive functioning for the ipsilateral hemisphere and, although to a lesser extent, for the contralateral hemisphere. We conclude that a single symptomatic lacunar infarct in the white matter is associated with (distant) disturbances in neurometabolites and that this decrease is related to a reduced cognitive capacity.