The metabolic syndrome (MetS) is associated with an increased incidence of diabetes and coronary heart disease. Postprandial lipemia is a prominent feature of dyslipidemia in both type 2 diabetes mellitus and MetS and is also associated with coronary heart disease. Oxidative stress and inflammation are pivotal in all stages of atherosclerosis; however, there is a paucity of data on postprandial oxidative stress and inflammation in subjects with MetS. Thus, the primary aim of this study was to compare the postprandial effects of an energy-dense, high-fat, fast-food-style (FFS) meal with an American Heart Association (AHA)-recommended heart-healthy meal on biomarkers of oxidative stress and inflammation in subjects with MetS. A total of 11 subjects with MetS completed the study. Glucose levels were significantly increased 2 hours after both FFS and AHA diets (P < .0001), and high-density lipoprotein cholesterol levels significantly decreased in FFS diet but not in the AHA diet (P for interaction < .05). Total triglyceride levels significantly increased postprandially only in the FFS meal but not in the AHA meal (P for interaction = .03). Plasma thiobarbituric acid reactive substances and malondialdehyde + hydroxynonenal increased significantly with time in both dietary groups, and the postprandial increase was greater in the FFS diet compared to the AHA diet (P < .0005). Serum high-sensitivity C-reactive protein, interleukin 6, and tumor necrosis factor levels did not change with time or dietary treatment. The postprandial increase in interleukin 1b was significantly higher with the FFS meal, thus resulting in significant differences between both treatments (P for interaction = .03). Thus, in subjects with MetS, consumption of an energy-dense, fatty meal (FFS breakfast) results in increased postprandial oxidative stress compared to a heart-healthy meal (AHA).