Graphical Abstract: The binding of para-Sulphonato-calix[4]arene to a series of Serum Albumin Proteins has been studied using Electrospray Mass Spectrometry, each protein shows different capacities to interact with para-Sulphonato-calix[4]arene, including the number of ligands bound, the Association Constants observed, and the stoichiometries at which the onset of each binding event is observed.