The immunolocalization of oxidized low-density lipoproteins (ox-LDL), β2-glycoprotein I (β2GPI), CD4+/CD8+ immunoreactive lymphocytes, and immunoglobulins in atherosclerotic lesions strongly suggested an active participation of the immune system in atherogenesis. Oxidative stress leading to ox-LDL production is thought to play a central role in both the initiation and progression of atherosclerosis. ox-LDL is highly proinflammatory and chemotactic for macrophage/monocyte and immune cells. Enzyme-linked immunosorbent assays (ELISAs) to measure circulating ox-LDL have been developed and are being currently used to assess oxidative stress as risk factor or marker of atherosclerotic disease. ox-LDL interacts with β2GPI and circulating ox-LDL/β2GPI complexes have been demonstrated in patients with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). It has been postulated that β2GPI binds ox-LDL to neutralize its proinflammatory and proatherosclerotic effects. Because β2GPI is ubiquitous in plasma, its interaction with ox-LDL may mask oxidized epitopes recognized by capture antibodies potentially interfering with immunoassays results. The measurement of ox-LDL/β2GPI complexes may circumvent this interference representing a more physiological and accurate way of measuring ox-LDL.