A 13-week feeding trial was carried out with juvenile rainbow trout to test two diets: a control diet without astaxanthin (AX) supplementation (CTRL diet), and a diet supplemented with 100 mg/kg of synthetic AX (ASTA diet). During the last week of the feeding trial, fish were exposed to episodic hyperoxia challenge for 8 consecutive hours per day. Episodic hyperoxia induced physiological stress responses characterized by a significant increase in plasma cortisol and hepatic glycogen and a decrease in plasma glucose levels. The decrease of plasma glucose and the increase of hepatic glycogen content due to episodic hyperoxia were emphasized with the ASTA diet. Hyperoxia led to an increase in thiobarbituric acid-reactive substances in the muscle, diminished by dietary AX supplementation in both liver and muscle. Muscle and liver AX were increased and decreased respectively after 7-day episodic hyperoxia, leading to an increase in flesh redness. This augment of muscle AX could not be attributed to AX mobilization, since plasma AX was not affected by hyperoxia. Moreover, hyperoxia decreased most of antioxidant enzyme activities in liver, whereas dietary AX supplementation specifically increased glutathione reductase activity. A higher mRNA level of hepatic glutathione reductase, thioredoxin reductase, and glutamate-cysteine ligase in trout fed the ASTA diet suggests the role of AX in glutathione and thioredoxin recycling and in de novo glutathione synthesis. Indeed, dietary AX supplementation improved the ratio between reduced and oxidized glutathione (GSH/GSSG) in liver. In addition, the ASTA diet up-regulated glucokinase and glucose-6-phosphate dehydrogenase mRNA level in the liver, signaling that dietary AX supplementation may also stimulate the oxidative phase of the pentose phosphate pathway that produces NADPH, which provides reducing power that counteracts oxidative stress. The present results provide a broader understanding of the mechanisms by which dietary AX is involved in the reduction of oxidative status. very much linked to oxidative stress, which is the result of an imbalance between the production of reactive oxygen (ROS) and nitrogen species (RNS) by cell respiration and immune responses, and the state of the antioxidant defenses [1]. In order to protect against oxidative stress, organisms have developed antioxidant systems consisting of low-molecular-mass compounds including glutathione, ascorbic and uric acid, tocopherols, and carotenoids, and high-molecular-mass proteins including superoxide dismutases, catalases, Se-dependent glutathione peroxidases, glutathione reductase, and glucose-6-phosphate dehydrogenase [2].Carotenoids are natural pigments with immune-stimulant and antioxidant properties [3,4] and are present in the integument of many vertebrate species, generating bright-colored traits [5] Among carotenoids, astaxanthin (AX) is the most commonly used feed additive in order to achieve the characteristic red-pink coloration in crustaceans and salmonids [6,7]. The red coloration of AX is due ...