The postprandial state seems to have a direct influence on oxidative status and insulin resistance. We determined the effect of an increase in plasma triglycerides after a high‐fat meal on oxidative stress in severely obese patients with differing degrees of insulin resistance. The study was undertaken in 60 severely obese persons who received a 60‐g fat overload with a commercial preparation. Measurements were made of insulin resistance, the plasma activity of various antioxidant enzymes, the total antioxidant capacity (TAC) and the plasma concentration of thiobarbituric acid reactive substances (TBARS). The patients with greater insulin resistance had a lower plasma superoxide dismutase (SOD) activity (P < 0.05) and a greater glutathione peroxidase (GSH‐Px) activity (P < 0.05). The high‐fat meal caused a significant reduction in SOD activity and an increase in the plasma concentration of TBARS in all the patients. Only the patients with lower insulin resistance experienced a significant increase in plasma catalase activity (2.22 ± 1.02 vs. 2.93 ± 1.22 nmol/min/ml, P < 0.01), remaining stable in the patients with greater insulin resistance. These latter patients had a reduction in plasma TAC (6.92 ± 1.93 vs. 6.29 ± 1.80 mmol/l, P < 0.01). In conclusion, our results show a close association between the degree of insulin resistance and markers of oxidative stress, both before and after a high‐fat meal. The postprandial state causes an important increase in oxidative stress, especially in severely obese persons with greater insulin resistance. However, we are unable to determine from this study whether there is first an increase in oxidative stress or in insulin resistance.