We demonstrate that the instability of the Sb vacancy in GaSb leads to a further increase in the acceptor-type defect concentration in proton irradiated undoped, p-type GaSb. Using positron annihilation spectroscopy in situ with 10 MeV proton irradiation at 35 K, we find that the irradiation produces both native vacancy defects in GaSb. However, the Sb vacancy is unstable above temperatures of 150 K and undergoes a transition resulting in a Ga vacancy and a Ga antisite. The activation energy of this transition is determined to be 0.6 eV ± 0.1 eV. Our results are in line with the established amphoteric defect model and prove that the instability of the Sb vacancy in GaSb has a profound role on the native defect concentration in GaSb.