Increased oxidation of low density lipoprotein (LDL) is characteristic of atherosclerosis. In this frame, high density lipoproteins (HDL) play an important role, being able to remove lipid peroxides (LPOs) and cholesterol from oxidized LDL, so exhibiting a protective role against atherosclerosis. A wide range of reactive compounds lead to the oxidation of methionine (Met) residues with the formation of methionine sulphoxide (MetO) in apolipoprotein A-I (ApoA-I). Consequently, the determination of MetO level can give both an evaluation of oxidative stress and the reduced capability of ApoA-I in LPOs and cholesterol transport. For these reasons, the development of analytical methods able to determine the MetO level is surely of interest, and we report here the results obtained by MALDI mass spectrometry. Copyright © 2013 John Wiley & Sons, Ltd.