The superoxide dismutase (SOD)-mimetic activities of copper complexes of a series of salicylic acid (SA) analogs were tested and compared to the activity of bovine erythrocyte SOD using ferricytochrome c reduction assay. Stability constants of copper complexes were measured potentiometrically using SCOGS2 program. In the presence of 10 g/ℓ albumin, all the copper complexes lost their SOD mimetic activities. Multiple regression analysis was employed for the statistical comparisons between the SOD mimetic activity and their physicochemical properties. Correlation exists for the SOD mimetic activity and steric parameter (E_s) and/or electronic parameter (Σσ) in xanthine/xanthine oxidase (XOD) system, demonstrating that E_s plays a key role in SOD activity whereas Σσ influences it to a lesser extent. The protective effect of copper complexes against membrane damage was measured by counting D-glucose released frm EGs. D-glucose and XOD were entrapped within EGs and acetaldehyde was used as a substrate for XOD. In this membrane model system using EGs, hydrophobic parameter (Σπ) is of most importance, producing parabolic equation while E_s and Σσ appear to play a minor role in protection against D-glucose release. In summary, to design an efficient SOD mimetic, stability, steric factor, lipophilicity and redox potential should be considered.