Cognitive reserve (CR) defines the capacity of the adult brain to cope with pathology in order to minimize symptomatology. Relevant lifetime social, cognitive and leisure activities represent measurable proxies of cognitive CR but its underlying structural and functional brain mechanisms remain poorly understood. We investigated the relationship between CR and regional gray matter volumes and brain activity (fMRI) during a working memory task in a sample of healthy elders. Participants with higher CR had larger gray matter volumes in frontal and parietal regions. Conversely, a negative correlation was observed between CR and fMRI signal in the right inferior frontal cortex, suggesting increased neural efficiency for higher CR individuals. This latter association however disappeared after adjusting for gray matter images in a voxel-based manner. Altogether, present results may reflect both general and specific anatomofunctional correlates of CR in the healthy elders. Thus, whereas heteromodal anterior and posterior gray matter regions correspond to passive (i.e. morphological) correlates of CR unrelated to functional brain activation during this particular cognitive task, the right inferior frontal area reveals interactions between active and passive components of CR related to the cognitive functions tested in the fMRI study.