The ability of the anesthetics metomidate hydrochloride and tricaine methanesulfonate (MS-222) to mitigate the cortisol stress response of Channel Catfish Ictalurus punctatus was evaluated during a 10-min confinement stress. The cortisol concentrations of Channel Catfish anesthetized in metomidate hydrochloride remained consistent throughout the 10-min exposure; however, for fish anesthetized with MS-222 and nonanesthetized fish, cortisol concentrations were approximately 7- and 22-fold higher, respectively, than the baseline concentrations. While both anesthetics reduced cortisol concentrations relative to those of nonanesthetized fish, these results suggest that MS-222 is an appropriate anesthetic to use during the initial 5 min of sedation and that metomidate hydrochloride is appropriate for longer periods of sedation.