Fundamental thermodynamic investigations have been carried out regarding the phase equilibria of La0.8Sr0.2MnO3±δ (LSM), a cathode of a solid oxide fuel cell (SOFC), utilizing the CALculation of PHAse Diagram (CALPHAD) approach. The assessed thermodynamic databases developed for LSM perovskite in contact with YSZ fluorite and the other species have been discussed. The application of computational thermodynamics to the cathode is comprehensively explained in detail, including the defect chemistry analysis as well as the quantitative Brouwer diagrams, electronic conductivity, cathode/electrolyte interface stability, thermomechanical properties of the cathode and the impact of gas impurities, such as CO2 as well as humidity, on the phase stability of the cathode. The quantitative Brouwer diagrams for LSM at different temperatures are developed and the detailed analysis of the Mn3+ charge disproportionation behavior and the electronic conductivity in the temperature range of 1000-1200°C revealed a good agreement with the available experimental observations. The effects of temperature, CO2 partial pressure, O2 partial pressure, humidity level and the cathode composition on the formation of secondary phases have been investigated and correlated with the available experimental results found in the literature. It has been indicated that the CO2 exposure does not change the electronic/ionic carriers’ concentration in the perovskite phase. The observed electrical conductivity drop is predicted to occur due to the formation of secondary phases such as LaZr2O7, SrZrO3, SrCO3 and Mn oxides at the LSM/YSZ interface, resulting in the blocking of the electron/ion transfer paths. For the thermo-mechanical properties of LSM, a new weight loss Mechanism for (La0.8Sr0.2)0.98MnO3±δ using the La-Sr-Mn-O thermodynamic database is modeled with respect to the compound energy formalism model. This newly proposed mechanism comprehensively explains the defect formation as a result of volume/weight change during the thermal cycles. According to the proposed mechanism the impact of cation vacancies regarding the volume change of cathode was explained.