The effect of edema on metabolic changes in contrast-enhancing multiple sclerosis lesions was studied by combining quantification of proton MR spectra with segmentation of the volume-of-interest, which was based on biexponential T2 relaxation. All lesions showed a second component (slong) with a longer T2 (185–450 ms), which was increased compared to healthy controls. Regression analysis indicated that slong replaces the short-T2 component and total creatine. Since the water content was close to 100%, slong was used to correct for an increase in extracellular space. This compensated for the apparent loss of creatine and rendered cholines markedly increased, as observed in animals with experimental allergic encephalomyelitis. Total N-acetyl aspartate (NAA) concentration was inversely correlated with slong and between 34–70% of its average reduction was assigned to edema. Thus, NAA loss exceeded cellular loss. Assessment of varying degrees of edema may be especially beneficial for quantitative longitudinal studies. Magn Reson Med 46:256–263, 2001. © 2001 Wiley-Liss, Inc.