A series of electrochemical impedance experiments have been carried out in order to investigate the effect of cell chemical composition on the determination of electrochemical characteristics of strontium-doped rare earth cobaltite cathodes. The impedance responses at different electrode potentials of the half-cell and symmetric single-cell setups are compared and analyzed by the equivalent circuit modeling method. The deconvolution of impedance spectra for single cells has been achieved by differential derivative of impedance real part versus ac frequency plot analysis method. The performance of electrolyte-supported Ni/Ce0.9Gd0.1O2-δ|Ce0.9Gd0.1O2-δ|Ln0.6Sr0.4CoO3-δ symmetric single-cells has been optimized for anode diffusion layer porosity, anode functional layer starting powder specific surface area (SBET,powder), and cobaltite-based cathode material composition in a single designed experiment according to the so-called response surface methodology. The combination of electrochemical impedance spectroscopy, equivalent circuit fitting, and mathematical statistics methods proved to be a powerful tool for interpreting solid oxide fuel cell data.