Carotid plaque is an aggregate marker of exposure to vascular risk factors, which are linked to structural brain changes. We investigated prestroke global and regional changes in brain volume in a carotid plaque population of cognitively healthy individuals and the association between carotid plaque characteristics and these changes.A total of 76 participants were divided into healthy control (HC, n = 28), vulnerable plaque (n = 27) and stable plaque groups (n = 21). All subjects underwent carotid ultrasound and brain magnetic resonance imaging (MRI). Voxel-based morphometry (VBM) was used to examine differences in regional gray matter volumes (rGMVs) among the different groups.The plaque group had a significantly lower mean total cerebral brain volume (TCBV) than the HC group (P = .03). Carotid intima-media thickness (CIMT) was negatively correlated with TCBV (r = -0.311, P = .006) and rGMV in the right thalamus (r = -0.589, P = .001). The rGMVs of the right middle occipital gyrus and bilateral lingual gyrus were significantly different between the unstable and stable groups. The gray-scale median (GSM) of the plaque and the total plaque risk score (TPRS) were correlated with the volume of the right middle occipital gyrus (r=-0.478, P = .001; r = 0.541, P = .001) and bilateral lingual gyrus (r = -0.419, P = .003; r = 0.288, P = .04).Carotid plaque is related to the volume of the brain parenchyma and right thalamus. The rGMVs of the right middle occipital gyrus and bilateral lingual gyrus differed between the vulnerable plaque and stable plaque groups, and the characteristics of carotid plaques may serve as indexes that reflect these changes.