Bone growth may occur in spaceflight as a response to skeletal unloading and head-ward fluid shifts. While unloading causes significant loss of bone mass and density in legs of animals exposed to microgravity, increased blood and interstitial fluid flows accompanying microgravity-induced fluid redistribution may elicit an opposite effect in the head. Seven 23-week-old, adult female wild-type C57BL/6 mice were randomly chosen for exposure to 15 days of microgravity on the STS-131 mission, while eight female littermates served as ground controls. Upon mission completion, all 15 murine calvariae were imaged on a micro-computed tomography scanner. A standardized rectangular volume was placed on the parietal bones of each calvaria for analyses, and three parameters were determined to measure increased parietal bone volume: bone volume (BV), average cortical thickness (Ct.Th), and tissue mineral density (TMD). Microgravity exposure caused a statistically significant increase in BV of the spaceflight (SF) group compared to that of the ground control (GC) group, the mean BV ± SD for the SF group was 1.904 ± 0.842 mm3, compared to 1.758 ± 0.122 mm3 for the GC group (p less than 0.05). Ct.Th demonstrated a trend of increase from 0.099 ± 0.006 mm in the GC group to 0.104 ± 0.005 mm in the SF group (p equals 0.12). TMD was similar between the two groups with 0.878 ± 0.029 g/cm3 for the GC group and 0.893 ± 0.028 g/cm3 for the SF group (p equals 0.31). Our results indicate that microgravity causes responsive changes in calvarial bones that do not normally bear weight. These findings suggest that fluid shifts alone accompanying microgravity may initiate bone adaptation independent of skeletal loading by tissue. This dataset was derived from the literature, and contains only grouped mCT data from the calvaria.