Obesity, as compared to normal weight, is associated with detectable structural differences in the brain. To the best of our knowledge, no previous study has examined the association of physical fitness with gray matter volume in overweight/obese children using whole brain analyses. Thus, the aim of this study was to examine the association between the key components of physical fitness (i.e. cardiorespiratory fitness, speed-agility and muscular fitness) and brain structural volume, and to assess whether fitness-related changes in brain volumes are related to academic performance in overweight/obese children. A total of 101 overweight/obese children aged 8–11 years were recruited from Granada, Spain. The physical fitness components were assessed following the ALPHA health-related fitness test battery. T1-weighted images were acquired with a 3.0 T S Magnetom Tim Trio system. Gray matter tissue was calculated using Diffeomorphic Anatomical Registration Through Exponentiated Lie algebra (DARTEL). Academic performance was assessed by the Batería III Woodcock-Muñoz Tests of Achievement. All analyses were controlled for sex, peak high velocity offset, parent education, body mass index and total brain volume. The statistical threshold was calculated with AlphaSim and further Hayasaka adjusted to account for the non-isotropic smoothness of structural images. The main results showed that higher cardiorespiratory fitness was related to greater gray matter volumes (P < 0.001, k = 64) in 7 clusters with β ranging from 0.493 to 0.575; specifically in frontal regions (i.e. premotor cortex and supplementary motor cortex), subcortical regions (i.e. hippocampus and caudate), temporal regions (i.e. inferior temporal gyrus and parahippocampal gyrus) and calcarine cortex. Three of these regions (i.e. premotor cortex, supplementary motor cortex and hippocampus) were related to better academic performance (β ranging from 0.211 to 0.352; all P < 0.05). Higher speed-agility was associated with greater gray matter volumes (P < 0.001, k = 57) in 2 clusters (i.e. the inferior frontal gyrus and the superior temporal gyrus) with β ranging from 0.564 to 0.611. Both clusters were related to better academic performance (β ranging from 0.217 to 0.296; both P < 0.05). Muscular fitness was not independently associated with greater gray matter volume in any brain region. Furthermore, there were no statistically significant negative association between any component of physical fitness and gray matter volume in any region of the brain. In conclusion, cardiorespiratory fitness and speed-agility, but not muscular fitness, may independently be associated with greater volume of numerous cortical and subcortical brain structures; besides, some of these brain structures may be related to better academic performance. Importantly, the identified associations of fitness and gray matter volume were different for each fitness component. These findings suggest that increases in cardiorespiratory fitness and speed-agility may positively influence the development of distinctive brain regions and academic indicators, and thus counteract the harmful effect of overweight and obesity on brain structure during childhood.