The present work elucidated and compared the energetics of the interaction of the food colourant tartrazine with two serum proteins. The binding affinity of tartrazine was higher to BSA than to HSA. The binding reaction was driven by a large negative standard molar enthalpic contribution. The stoichiometry values showed that a 1:1 complexation occurred between tartrazine and thetwoserumalbumins,regardlessofthetemperatureandthesalt concentrations.Thebindingaffinityvaluesdecreasedwithincrease in ionic strength of the medium, which established the involvementof polyelectrolyticforcesinthe complexationprocess. Nevertheless, the polyelectrolytic component accounted for only 6–18% of the total standardmolar Gibbsenergychange inthe salt concentration range investigated. Negative values of the standard molar heat capacity, in conjunction with enthalpy–entropy compensation, clearly suggested the involvement of dominant hydrophobic forces in the complexation process. DSC studies revealed that tartrazine binding stabilized the serum albumins. These studies provide a detailed account of the energetics of the interaction of tartrazine with serum proteins which may be useful in assessing the toxic effects of this food colourant.