Aquatic organisms in their natural environment alternate periods of feeding and fasting in response to several factors (e.g. temperature, spawning migration, reproduction, etc.). To survive these periods of food deprivation fish mobilize their energy reserves and potentially readjust their metabolic capacities. These metabolic adjustments impose changes in swimming performance that would decrease the capacity of wild fish to catch food, therefore accentuating the decline in energetic status. Starvation has been reported to have pro-oxidant effects, and both the inadequate neutralization of the reactive oxygen species (ROS) generated by oxidative metabolism and the reduced level of antioxidant defenses, both enzymatic and non-enzymatic, may be responsible for some of the detrimental effects of starvation. The depression in protein synthesis induced under unfavorable feeding conditions reduces the levels of enzymes involved in the direct neutralization of ROS and in the recycling of important antioxidant molecules, such as glutathione. Also, non-enzymatic antioxidants provided by food, such as vitamins C and E, are not available to protect the aquatic organisms from the oxidative attack by non-neutralized ROS. When the rate of ROS generation exceeds that of their removal, oxidative stress occurs. Its deleterious effects include oxidation of proteins, DNA, and steroid components, as well as peroxidation of unsaturated lipids in cell membranes. Together these effects lead to reversible or irreversible cell damage, and eventually to cell death. However, unlike mammals, fish possess a great ability to survive these conditions. The aim of this chapter is to give an overview of the influence of food deprivation on the metabolic status and antioxidant defenses of fish.