It has been reported that high-fat, high-carbohydrate (HFHC) meals increase oxidative stress and inflammation. We examined whether repeated intake of excess energy in the form of HFHC meals alters reactive oxygen species (ROS) generation and the expression levels of antioxidant enzymes and mitochondrial proteins in mononuclear cells, and to determine whether this is associated with insulin resistance. We recruited healthy lean individuals (n 10). The individuals were divided into two groups: one group (n 5) ingested 10878·4 kJ/d (2600 kcal/d; 55-70 % carbohydrate, 9·5-16 % fat, 7-20 % protein) recommended by the Dietary Reference Intake for Koreans for 4 d and the other group (n 5) ingested a HFHC meal containing 14 644 kJ/d (3500 kcal/d). Then, measurements of blood insulin and glucose levels, together with suppressor of cytokine signalling-3 (SOCS-3) expression levels, were performed in both groups. Also, cellular and mitochondrial ROS levels as well as malondialdehyde (MDA) levels were measured. Expression levels of cytosolic and mitochondrial antioxidant enzymes, and mitochondrial complex proteins were analysed. Repeated intake of HFHC meals induced an increase in homeostasis model of assessment-insulin resistance (HOMA-IR), together with an increase in SOCS-3 expression levels. While a single intake of the HFHC meal increased cytosolic and mitochondrial ROS, repeated intake of HFHC meals reduced them and increased the levels of MDA, cytosolic and mitochondrial antioxidant enzymes, and several mitochondrial complex proteins. Repeated intake of HFHC meals induced cellular antioxidant mechanisms, which in turn increased lipid peroxidation (MDA) and SOCS-3 expression levels, induced hyperinsulinaemia and increased HOMA-IR, an index of insulin resistance. In conclusion, excess energy added to a diet can generate detrimental effects in a short period.