The defect chemistry of foreign transition metals in perovskite oxides was investigated by first-principles calculations with focus on Ni and Zn in Y-doped BaZrO3. Additional transition metals (Cu, Fe, Pd, Pt, and Ag) and perovskites (SrZrO3 and SrTiO3) were considered for comparison. The octahedral interstice coordinated with square-planar oxygen could accommodate smaller cations and Ni2+ was found to be the most stable, particularly in the presence of barium vacancies. Significant solubility of Ni was substantiated only for nominally A-site deficient materials under oxidizing conditions. The computational results were corroborated by experimental studies on BaZr0.85Y0.15O3−δ with 4 mol% NiO or ZnO sintering additives. While synchrotron radiation X-ray powder diffraction of the Ni containing sample showed the presence of a BaY2NiO5 secondary phase, it could not account for the nominal amount of Ni in the sample. STEM and EDS analyses of both the Zn and Ni containing samples showed that Zn accumulated in the grain boundaries while Ni was evenly distributed within the grains and grain boundaries indicating that Ni was dissolved in the BaZrO3 structure. Furthermore, metallic Ni particles appeared on the sample surface after treatment under reducing conditions in accordance with computational predictions. The influence of interstitially dissolved Ni on proton conductivity was evaluated based on trapping of protons. Barium vacancies were found to be strong proton traps, with a binding energy of −0.80 eV, while the binding energy of protons associated with adjacent Ni interstitials was reduced to −0.20 eV.