<p>This study investigated the impact of a high-carbohydrate diet on the response to skin wounding in red seabream (<i>Pagrus major</i>), with a focus on oxidative stress and intestinal health. Triplicate groups of fish (<i>n</i> = 40 per tank) were fed either a control diet (CC, 15% carbohydrate) or a high-carbohydrate diet (HC, 25% carbohydrate) for 8 weeks, followed by a standardized skin-wounding challenge. The HC diet induced hyperglycemia, increased hepatic oxidative stress, and caused intestinal impairments before wounding. These effects were significantly exacerbated after skin wounding. Compared with the CC group, HC-fed fish showed significantly lower activities of hepatic antioxidant enzymes, together with further elevations in oxidative damage. In the intestine, the HC diet caused pronounced downregulation of antioxidant genes and mucins, accompanied by a reduction in mucous goblet cells. The impaired mucin layer, associated with reduced polypeptide N-acetylgalactosaminyltransferase 13 expression, together with the downregulation of perforin 1 and antimicrobial peptides, facilitated increased bacterial invasion of the intestinal mucosa. The HC diet further compromised intestinal integrity by reducing the expression of tight junction protein 2 alpha and 3, as well as increasing intestinal permeability, as indicated by elevated serum diamine oxidase levels. In conclusion, a high-carbohydrate diet exacerbates skin wound-induced oxidative stress and intestinal barrier dysfunction by impairing antioxidant defense, mucin synthesis, antimicrobial protection, and tight junction integrity. These changes ultimately reduce survival and highlight the negative impact of excessive dietary carbohydrate on the ability of carnivorous fish to cope with physical stress.</p> Graphical Abstract <p></p>