Human serum albumin (HSA) is the main transport protein in human plasma and also contains the most abundant thiol group in this fluid at its C34 residue. In its structure, HSA contains a number of binding sites with various degrees of specificity for the species the protein transports. Plasmatic calcium is bound to HSA in 40% and its binding affects some structural and electrostatic properties of the protein. Of particular importance, the binding of calcium modifies the pH of the neutral to basic conformational transition, that occurs slightly above neutral pH, that has a physiologic relevance and in which the reactivity of the single thiol is also involved. Our hypothesis is that Ca²⁺ binding affects the reactivity of the thiol group, particularly toward anionic oxidants, both by electrostatic interactions and by structural modification that might alter the solvent and oxidant accessibility to the sulfur. To study this we characterize the kinetics of thiol oxidation by anionic (5,5'-dithiobis(2-nitrobenzoate), DTNB) and neutral (2,2'-dithiodipyridine, DTPy) disulfides, and by neutral and anionic oxidants. These kinetics experiments are performed in the presence o absence of 2.4 mM Ca²⁺. Our results show that the presence of Ca²⁺ affects both the pH independent rate constant of oxidation and the pH profile of oxidation by DTNB but has a minimal effect on the reactivity toward DTPy. The pH profiles for DTNB and DTPy are similar in the presence of Ca²⁺, but differ in it absence. Current experiments are aimed to dissect the electrostatic from the structural/accessibility effects by use of smaller oxidants (H₂O₂ and ONOO^-) and other multivalent cations (Mg²⁺, Co(en)3³⁺) that differ from Ca²⁺ in their specific binding to HSA.