In this work we analyze the effects of the weak acid content of macroporous cation exchange resins based on acrylamido and vinyl polymers that contain different amounts of weak acid groups in addition to their main sulphopropyl cation exchange functionality. UNOsphere S and Rapid S resins from Bio-Rad Laboratories are used for this comparison. When operated at pH values below 7, the presence of weak acid groups in UNOsphere S results in substantial pH transients, which are induced by changes in salt concentration, even though the mobile phase is buffered. These transients are greatly reduced with UNOsphere Rapid S, which contains a much lower concentration of weak acid groups, permitting very rapid requilibration and avoiding any significant change in pH during protein elution with salt. Protein adsorption equilibrium and mass transfer rates were also studied for both materials using several proteins with molecular masses between 15 and 150 kDa. Despite its much lower concentration of weak acid groups, UNOsphere Rapid S exhibits protein adsorption capacities and effective pore diffusivities that are essentially the same as those observed for UNOsphere S. These results suggest that the weak acid groups in UNOsphere S are primarily associated with the polymer backbone structure and do not interact directly with proteins molecules.