Objective: Better prediction of tissue prognosis in acute stroke might improve treatment decisions. We hypothesized that there are metabolic ischemic disturbances measurable non-invasively by proton MR spectroscopy (1HMRS) that occur earlier than any structural changes visible on diffusion tensor imaging (DTI), which may therefore serve for territorial identification of “tissue at risk”. Methods: We performed multi-voxel 1HMRS plus DTI within a maximum of 26 hours, and DTI at three-seven days, after ischemic stroke. We compared choline, lactate, NAA, creatine concentrations in normal-appearing voxels that became infarcted("infarct expansion”), with normal-appearing voxels around the infarct that remained “healthy”(“non-expansion”) on follow-up DTI. Each “infarct expansion” voxel was additionally classified as either “complete infarct expansion”(infarcted tissue on follow-up DTI covered ≥50% of the voxel) or “partial infarct expansion”(<50% of voxel). Results: In 31 patients (NIHSS:0–28) there were 108 infarct "non-expansion” voxels and 113 infarct "expansion” voxels (of which 80 were “complete expansion” and 33 “partial expansion” voxels). Brain choline concentration increased for each change in expansion category from "non-expansion", via "partial expansion" to "complete expansion" (2423, 3843, 4158i.u.; p<0.05). Changes in lactate, NAA and creatine concentrations in expansion category were insignificant although for lactate there was a tendency to such association. Conclusions: Choline concentration measurable with 1HMRS was elevated in peri-ischemic normal-appearing brain that became infarcted by three-seven days. The degree of elevation was associated with the amount of infarct expansion. 1HMRS might identify DTI-normal appearing tissue at risk of conversion to infarction in early stroke.