Studies focusing on the interaction of dietary and acute emotional stress on oxidative stress in cortex frontal and in brain mitochondria are scarce. Dietary-induced insulin resistance, as observed in Western diets, has been associated with increased oxidative stress causing mitochondrial dysfunction. We hypothesized that acute emotional stress could be an aggravating factor by impacting redox status in cortex and brain mitochondria. Thus, the aim of the present study was to evaluate the combination of an insulin resistance inducing high-fat/high-fructose (HF/HFr) diet and acute emotional stress on brain oxidative stress in rats. We measured several oxidative stress parameters (carbonyls, FRAP, TBARS assays, GSH, GSSG, oxidized DNA, mRNA expression of redox proteins (Nrf2), and uric acid). The HF/HFr diet resulted in increased oxidative stress both in the brain mitochondria and in the frontal cortex and decreased expression of the Nrf2 gene. The emotional stress induced an oxidative response in plasma and in brain mitochondria of the control group. In the HF/HFr group it triggered an increase expression of the redox transcription factor Nrf2 and its downstream antioxidant genes. This suggests an improvement of the redox stress tolerance in response to an enhanced production of reactive oxygen species. Accordingly, a blunted oxidative effect on several markers was observed in plasma and brain of HF/HFr-stressed group. This was confirmed in a parallel study using lipopolysaccharide as a stress model. Beside the Nrf2 increase, the stress induced a stronger UA release in HF/HFr which could take a part in the redox stress.