Chronic stress is the principal component to many human and animal disorders. As stress responses are remarkably conserved between mammals and teleosts, the use of teleosts in comparative models has been a useful tool in neurobiology. In particular, salmonid fishes have emerged as model organisms for chronic social stress due to their well-characterized social behavior and physiology. The serotonergic system is involved in a wide variety of functions, among which are the control of the neuroendocrine stress response and the regulation of an array of behaviors such as feeding and aggression. In salmonid models of chronic social stress, serotonergic activity in subordinate individuals has been found to be elevated in many brain regions, in some instances to pathological levels. In this study, the serotonergic system of Atlantic salmon was pharmacologically activated with fluoxetine for 18 days and the behavioral, physiological and neurochemical responses were examined. Fluoxetine induced anorexia, surfacing behavior and an increased tendency for treated fish to position themselves in a head up, tail down position. Physiologically, fluoxetine treated salmon had increased brain stem serotonergic and norepinephrine activity, greatly elevated cortisol levels, larger relative heart sizes, upregulated hypothalamic AVT and 5-HT1Aβ receptor mRNA levels. All of these behavioral and physiological parameters are strikingly similar to those exhibited by subordinate salmonids in chronic social stress models. These results indicate that long term pharmacological activation of the serotonergic system in Atlantic salmon recapitulates many of the typical behavioral and physiological markers found in salmonid models of chronic social stress. The utilization of fluoxetine and other pharmacological tools to manipulate serotonergic signaling may thus be of further use in elucidating the intricacies of the stress response and mechanisms that lead to its dysfunction.