The role of cell death in atherosclerosis remains ill-defined, however, a growing body of evidence suggests that cell death stimulates atherogenesis through the induction of inflammation and enlargement of the necrotic core. Although there is solid evidence to suggest that lipid oxidation and toxicity are linked, indications that protein oxidation may play an important role in cytotoxicity are numerous. The abundance of dead cells in atherosclerotic plaques and their co-localization with HOCl-modified proteins provides an opening for the suggestion that the products of protein oxidation may be at the heart of oxLDL-induced cell death. Examination of the modification of LDL and albumin by HOCl, and the cytotoxicity of these oxidised molecules were the focus of this study, along with the elucidation of their cell death mechanisms toward U937 cells. Measurement of lipid peroxidation markers, TBARS and 7-ketocholesterol, showed no significant increase in HOCl-oxLDL compared to native levels although all α-tocopherol had been lost. In contrast there was a large loss of tyrosine, of which a small percentage went to dityrosine, indicating that the protein moiety of LDL was the main target of HOCl attack. Albumin became fragmented and smeared on SDS-PAGE gels with increasing HOCl/BSA molar ratios. In addition there was significant reduction in tyrosine levels and a small increase in dityrosine. Both HOCl-oxLDL and oxidised albumin (oxALB) caused concentration-dependent cell viability loss in U937 cells following a significant drop in intracellular GSH concentration, coinciding with a peak in oxidative stress. Removal of chloramines with methionine significantly reduced the toxicity of oxALB, but at higher concentrations this effect was reduced. This was in contrast to HOCl-oxLDL where the removal of chloramines had no effect on its toxicity. Morphological observations of cell swelling, cell membrane integrity loss and rupture, along with flow cytometry results indicate that U937 cells underwent necrosis, but only after intracellular GSH was lost. Intracellular GSH and cell viability loss were prevented by 200 μM extracellular 7,8-dihydroneopterin (78NP), indicating that 78NP scavenging of ROS generated in response to the oxidised proteins was sufficient to prevent cell death. This study demonstrates the cytotoxicity of HOCl-damaged LDL and albumin is likely due to a common oxidative product or structural motif which may be active within atherosclerotic plaques.