Abstract This study reports data on plasma clearance kinetics of anaesthetics concomitant with physiological stress responses in dorsal aorta (DA) cannulated Atlantic salmon ( Salmo salar) both with and without influence of artificial gill ventilation during recovery from anaesthesia. For MS-222 the plasma data were best described by a one-compartment open model and first-order elimination, whereas a two-compartment open model and first-order elimination best described the plasma data for benzocaine and isoeugenol. The compartment analysis was not affected by ventilation. Distribution volumes from 1.99 l kg − 1 (isoeugenol) to 3.98 (MS-222) and 5.12 l kg − 1 (benzocaine) showed a moderate to large distribution of the drugs from plasma to tissues. MS-222 was eliminated most rapidly, with an elimination half-life of 1.7 min, while elimination half-lives of 18.7 and 25 min were calculated for benzocaine and isoeugenol, respectively. Ventilation following exposure increased the elimination rate. Anaesthetics were administered in two steps with an initial 10 min of sedation by a low dosage (1 × 10 − 1 of full dosage) before moving the fish to a full strength anaesthesia bath. All anaesthetics used caused a marked increase in plasma cortisol, apparent already at the end of the exposure. Marked differences were noted between anaesthetics, with time to regain consciousness and responsiveness to external stimuli paralleling the plasma clearance of the anaesthetic. Recovery from anaesthesia was accompanied by higher respiration frequency. Recovery was always faster when the fish was given artificial gill ventilation.