Cognitive reserve (CR) contributes to inter-individual variability of cognitive performance and to preserve cognitive functioning facing aging and brain damage. However, brain anatomical and functional substrates of CR still need to be fully explored in young healthy subjects (HS). By evaluating a relatively large cohort of young HS, we investigated the associations between CR and structural and functional magnetic resonance imaging (MRI) measures in early adulthood.A global Cognitive Reserve Index (CRI), combining intelligence quotient, leisure activities and education, was measured from 77 HS and its brain anatomical and functional substrates were evaluated through a multiparametric MRI approach. Substrates of the three subdomains (cognitive/social/physical) of leisure activities were also explored.Higher global and subdomain CRIs were associated with higher gray matter volume of brain regions involved in motor and cognitive functions, such as the right (R) supplementary motor area, left (L) middle frontal gyrus and L cerebellum. No correlation with measures of white matter (WM) integrity was found. Higher global and subdomains CRIs were associated with lower resting-state functional connectivity (RS FC) of L postcentral gyrus and R insula in sensorimotor network, L postcentral gyrus in salience network and R cerebellum in the executive-control network. Moreover, several CRIs were also associated with higher RS FC of R cuneus in default-mode network.CR modulates structure and function of several brain motor and cognitive networks responsible for complex cognitive functioning already in young HS. CR could promote optimization of the recruitment of brain networks.