Ab initio embedded cluster calculations have been performed on Pr3+-doped Lu2O3, in order to investigate the mechanism responsible for the highly efficient 3P01D2 non-radiative relaxation experimentally observed. (PrO6)9− embedded clusters representing the C 2 and S 6 substitutional sites of Pr3+:Lu2O3 have been studied using wave function-based methods. It is found that an outward relaxation of the first coordination sphere around the impurity takes place upon doping. At the relaxed geometry of the lowest spin triplet 4f5d state, all the 4f5d states lie much higher in energy than all 4f 2 states (except the 1S multiplet). This result is in opposition to the interpretation of intersystem crossing through a low-lying 4f5d excited state of Pr3+ as the mechanism for the fast non-radiative 3 P 0 → 1 D 2 relaxation proposed in the literature. Absorption to the lowest spin triplet 4f5d state is calculated to be around 4,800 cm−1 higher for the C 2 site than for the S 6 site, supporting the assignment of bands in the excitation spectrum previously reported.