Several functional imaging studies have investigated the regional effects of sleep deprivation (SD) on impaired brain function; however, potential changes in the functional interactions between the cerebral hemispheres after SD are not well understood. In this study, we used a recently validated approach, voxel-mirrored homotopic connectivity (VMHC), to directly examine the changes in interhemispheric homotopic resting-state functional connectivity (RSFC) after SD. Resting-state functional MRI (fMRI) was performed in 28 participants both after rest wakefulness (RW) and a total night of SD. An interhemispheric RSFC map was obtained by calculating the Pearson correlation (Fisher Z transformed) between each pair of homotopic voxel time series for each subject in each condition. The between-condition differences in interhemispheric RSFC were then examined at global and voxelwise levels separately. Significantly increased global VMHC was found after sleep deprivation; specifically, a significant increase in VMHC was found in specific brain regions, including the thalamus, paracentral lobule, supplementary motor area, postcentral gyrus and lingual gyrus. No regions showed significantly reduced VMHC after sleep deprivation. Further analysis indicates that these findings did not depend on the various sizes of smoothing kernels that were adopted in the preprocessing steps and that the differences in these regions were still significant with or without global signal regression. Our data suggest that the increased VMHC might reflect the compensatory involvement of bilateral brain areas, especially the bilateral thalamus, to prevent cognitive performance deterioration when sleep pressure is elevated after sleep deprivation. Our findings provide preliminary evidence of interhemispheric correlation changes after SD and contribute to a better understanding of the neural mechanisms of SD.