Abstract Electrochemical properties are inherent to the techniques of electrophoresis and electrospray ionization. Interfacing capillary zone electrophoresis (CZE) with electrospray mass spectrometry (ESMS) can lead to the observation of oxidized species generated as a result of the electrochemical nature of this coupling. Using a nanoelectrospray (nES) interface combined with CZE, controlled chemical oxidation of peptides is demonstrated. The electrolysis of water is used to explain the origin of the chemically oxidized species and this is confirmed using experiments with 18O labeled water. Identification of the oxidized residues was possible using tandem mass spectrometry to sequence the modified peptides. Methionine was found to be the most readily oxidized residue, followed by aromatic amino acids. Surprisingly, oxidation of aliphatic residues (leucine) was also observed. Addition of a reducing agent to the CZE buffer was found to reduce, but not eliminate, the extent of oxidation. The electrochemical generation of protons at the electrosprayer was used to assist in the analysis of monophosphate nucleotides. Nucleotides were separated as anions followed by detection as [M + H] + ions.