Isothermal titration calorimetry allows the determination of thermodynamic parameters for the interaction between a protein and mono- or oligosaccharides in solution. For the study of protein–carbohydrate interactions, it is a robust way to determine the stoichiometry and affinity, as well as the enthalpic and entropic contributions to this interaction, without the use of labeled proteins or substrates. Here we describe a standard multiple-injection titration experiment for measuring the binding energetics between a carbohydrate-binding protein and an oligosaccharide.