Determine whether obstructive sleep apnea (OSA) subjects show indications of axonal injury. We assessed fiber integrity in OSA and control subjects with diffusion tensor imaging (DTI). We acquired four whole-brain DTI series from each subject. The four series were realigned, and the diffusion tensor calculated at each voxel. Fractional anisotropy (FA), a measure of fiber integrity, was derived from the diffusion tensor, resulting in a whole brain FA "map." The FA maps were spatially normalized, smoothed, and compared using voxel-based statistics to determine differences between OSA and control groups, with age as a covariate (P < 0.05, corrected for multiple comparisons). University medical center. We studied 41 patients with untreated OSA (mean age +/- SD: 46.3 +/- 8.9 years; female/male: 7/34) with apnea-hypopnea index 15 to 101 (mean +/- SD: 35.7 +/- 18.1 events/hour), and 69 control subjects (mean age +/- SD: 47.5 +/- 8.79 years; female/male: 25/44). Multiple regions of lower FA appeared within white matter in the OSA group, and included fibers of the anterior corpus callosum, anterior and posterior cingulate cortex and cingulum bundle, right column of the fornix, portions of the frontal, ventral prefrontal, parietal and insular cortices, bilateral internal capsule, left cerebral peduncle, middle cerebellar peduncle and corticospinal tract, and deep cerebellar nuclei. White matter is extensively affected in OSA patients; the alterations include axons linking major structures within the limbic system, pons, frontal, temporal and parietal cortices, and projections to and from the cerebellum.