This study was investigated adolescents’ brain changes of functional connectivity and cerebral cortical thickness with resting state fMRI during science learning using VR contents. High school students were administered science learning program consisted of 16 VR contents for four weeks. We analyzed the brain changes of the resting state functional connectivity and the cerebral cortex thickness before and after learning sessions. We interpreted subjects’ learning motivation, immersion, social interaction, addiction, dizziness through analyzing the brain data. The results have shown that the functional connectivities was increased between the orbital frontal cortex and pallidum, and the orbital frontal cortex and putamen, which were presumably interpreted that science learning with VR contents is involved in a positive motivation and reward system. There were also the increased connectivities between the inferior fontal gyrus and orbital frontal cortex, and middle cingulate cortex and thalamus, which should be related to the experienced immersion in students’ learning. Furthermore, this study was also observed the increased connectivities among precentral gyrus, middle temporal gyrus, inferior temporal gyrus, and paracentral lobule, which could be interrelated to dizziness with a gap between visual and body movements during VR learning. However, there was no change in the brain connectivity related to addiction and social interaction. These results were able to show the structural and functional changes in the brain level during science learning with VR contents. This study is proposed an implication that the increased VR contents in the classroom should be appropriately designed and provided for adolescents’ brain and emotional development.