The electronic properties of high-efficiency CuInSe2 (CIS)-based solar cells are affected by the microstructural features of the absorber layer, such as point defect types and their distribution. Recently, there has been controversy over whether some of the typical point defects in CIS—VCu, VSe, InCu, CuIn—can form stable complexes in the material. In this work, we demonstrate that the presence of defect complexes during device operational time can be justified by taking into account the thermodynamic and kinetic driving forces acting behind defect microstructure formation. Our conclusions are backed up by thorough state-of-the-art calculations of defect interaction potentials as well as the activation barriers surrounding the complexes. Defect complexes such as InCu−2VCu, InCu−CuIn, and VSe−VCu are shown to be stable against thermal dissociation at device operating temperatures, but can anneal out within tens of minutes at temperatures higher than 150–200 °C (VCu-related complexes) or 400 °C (antisite pair). Our results suggest that the presence of these complexes can be controlled via growth temperatures, which provides a mechanism for tuning the electronic activity of defects and the device altogether.