The physiological consequences of "premature migratory return" to freshwater for wild sea-run brown trout (Salmo trutta) smolts infested with sea lice (Lepeoplitheirus salmonis) were investigated in the laboratory. Osmoregulatory, metabolic, and stress markers were analysed in order to assess the potential consequences of transfer to freshwater, 19 days after the challenge with L. salmonis. Infestation intensity was significantly reduced following transfer to freshwater, and mortality rates were markedly higher in infested fish maintained in seawater vs. fish that were transferred to freshwater. Significant sea lice effects, consistent across a number of physiological markers, were apparent once L. salmonis developed to the mobile stages. Plasma chloride, lactate, and cortisol all were significantly higher than control values, and liver glycogen concentration was significantly reduced in infested fish in seawater. After return to freshwater, these physiological measures returned to control levels, but significant lice effects persisted for fish maintained in seawater. Premature return of infested sea-run brown trout to freshwater does, therefore, confer significant short-term physiological benefits across a range of osmoregulatory, metabolic, and stress markers.