A mild pro-oxidative state accompanies meal ingestion, which results in an increase in biomarkers of inflammation, adhesion, and endothelial dysfunction, all of which are factors in the development of cardiovascular disease. Both fat and carbohydrate can cause the effect, which is additive and exacerbated by diabetes. The presence of lipid, glucose, and cholesterol oxidation products of dietary or endogenous origin may contribute to postprandial oxidative stress. However, the generation of excess superoxide due to abundant energy substrate after the meal may be a predominate factor resulting in oxidative stress and a decrease in nitric oxide, which is important to endothelial function. Remediation of postprandial oxidative stress through direct reduction of superoxide generation and simultaneous consumption of antioxidants with each meal should be a focus of future research.