The dissociative chemisorption of HCl on clean and oxidized Cu(100) surfaces has been investigated using x-ray photoelectron spectroscopy (XPS) and scanning tunneling microscopy (STM). Whereas the dissociation of HCl at the clean surface is limited to the formation of a (√2×√2)-R45° Cl(a) monolayer, the presence of surface oxygen removes this barrier, leading to chlorine coverages up to twice that obtained at the clean surface. Additional features in the STM images that appear at these coverages are tentatively assigned to the nucleation of CuCl islands. The rate of reaction of the HCl was slightly higher on the oxidized surface but unaffected by the initial oxygen concentration or the availability of clean copper sites. Of the two distinct domains of adsorbed oxygen identified at room temperature on the Cu(100) surfaces, the (√2×√2)-R45° structure reacts slightly faster with HCl than the missing row (√2×2√2)-R45° O(a) structure. The results address the first stages in the formation of a copper chloride and present an interesting comparison with the HCl/O(a) reaction at Cu(110) surfaces, where oxygen also increased the extent of HCl reactions. The results emphasize the importance of the exothermic reaction to form water in the HCl/O(a) reaction on copper. Display omitted •HCl dissociation at clean and oxidised Cu(100) surface studied with XPS and STM.•(√2×√2)-R45° O(a) and (√2×2√2)-R45° O(a) imaged and recorded reacting with HCl.•Effects of O(a) concentration on HCl studied: clean copper surface sites not required.•O(a) accelerates formation of multilayer chlorides.•Reaction of HCl with high concentrations of oxygen shown to involve etching of oxide surface and nucleation of copper chlorides islands.