Structural neuroimaging studies have provided evidence of differences in local brain volume between cocaine-dependent and healthy control individuals. While sex differences in aetiology, course and brain dysfunction associated with chronic cocaine abuse have been previously documented, evidence of sex-specific differences in brain volume has not been examined thus far. This study examined sex-related differences in grey matter volume between cocaine-dependent and healthy control subjects using voxel-based morphometry. High-resolution T1 structural scans were obtained from 36 inpatient, treatment-engaged 3-week abstinent cocaine-dependent (CD) individuals. Fifty healthy control subjects were also scanned. Segmentation and registration were performed in SPM8, using New Segment and DARTEL, respectively. The whole-brain statistical analysis was conducted in SPM8 using random field-based cluster-size testing and family-wise error rate correction for multiple comparisons. CD patients were found to have less grey matter volume in anterior prefrontal cortex, including frontopolar and orbitofrontal cortices, and a posterior region surrounding the parietal-occipital sulcus. Female CD patients had less grey matter volume than female controls in left inferior frontal gyrus, insula, superior temporal gyrus and hippocampus. Male CD patients had less grey matter in a superior cortical region that included the precentral gyrus and the mid-cingulate. These sex differences in lower grey matter volume add to the evidence from functional neuroimaging for sex-specific differences in the neurophysiological changes associated with chronic cocaine use.