Obstructive sleep apnea (OSA) patients show compromised emotional and cognitive functions, including anterograde memory deficits. While some memory inadequacies in OSA may result from earlier-described structural deficits in the hippocampus, mammillary body injury also could contribute, since these structures receive projections from the hippocampus via the fornix, project heavily to the anterior thalamus, and have been implicated in other conditions with memory deficiencies, such as Korsakoff's syndrome. However, volume loss in mammillary bodies has not been reported in OSA, likely a consequence of logistic difficulties in size assessment. We evaluated mammillary body volumes in 43 OSA (mean age+/-S.D., 46.9+/-9.2 years; mean apnea-hypopnea-index+/-S.D., 31.2+/-19.9 events/h) and 66 control subjects (age, 47.3+/-8.9 years). Two high-resolution T1-weighted image volumes were collected on a 3.0 T magnetic resonance scanner, averaged to improve signal-to-noise, and reoriented (without warping) into a common space. Brain sections containing both mammillary bodies were oversampled, and the bodies were manually traced and volumes calculated. OSA patients showed significantly reduced left, right, and combined mammillary body volumes compared with control subjects, after partitioning for age, gender, and head size (multivariate linear model, p<0.05). Left-side mammillary bodies showed greater volume reduction than the right side. Diminished mammillary body volume in OSA patients may be associated with memory and spatial orientation deficits found in the syndrome. The mechanisms contributing to the volume loss are unclear, but may relate to hypoxic/ischemic processes, possibly assisted by nutritional deficiencies in the syndrome.