Al2O3 is a promising material for use as a dielectric in metal-oxide-semiconductor devices based on III-V compound semiconductors. However, the presence of deep levels and fixed charge in the Al2O3 layer is still a concern, with native defects being a possible cause of traps, leakage, and fixed charge. We report hybrid density functional calculations for vacancies, self-interstitials, and antisites in Al2O3. The energetic positions of defect levels are discussed in terms of the calculated band alignment at the interface between the oxide and relevant III-V materials. We find that oxygen vacancies are the defects most likely to introduce gap levels that may induce border traps or leakage current in a gate stack. In addition, both self-interstitials and aluminum vacancies introduce fixed charge that leads to increased carrier scattering in the channel and shifts the threshold voltage of the device.