The sluggishness of the O 2 reduction reaction (ORR) is the most significant challenge to fuel cell commercialization. Cu-based ORR catalysts are promising non-precious metal alternatives to Pt. In this study, we synthesize four different Cu 2+ complexes of tripeptides (Cu−GSHAmide, Cu−NCG, Cu−ECG, and Cu−QCG) and analyze the relationships between their electrocatalytic activities and physicochemical properties. Rotating ring-disk electrode experiments indicate that the catalytic current densities and selectivities vary widely as a function of pH and peptide identity. Through Fourier transform infrared spectroscopy, we describe the nature of the intermolecular forces between the peptides studied along with those of the corresponding Cu 2+ complexes. This analysis allows us to quantify the degree of peptide aggregation in the ORR electrocatalysts. Combined with the Cu 2+ −peptide binding constants, we develop models that accurately predict how peptide aggregation dictates catalyst current density and selectivity for the four-electron reduction of O 2 to water. These models indicate that Cu 2+ −peptide ORR electrocatalysts with relatively strong binding constants and weak peptide aggregation exhibit increased selectivity and enhanced kinetics. This central finding highlights an important set of design rules for the development of future highperformance Cu ORR electrocatalysts.