Fipronil is a phenylpyrazole insecticide widely used to control pests in agriculture even 29 though evidence of harmful side effects in non-target species has been reported. A 30 comprehensive study on the effects of dietary administration of Regent®800WG (80% 31 fipronil) in European sea bass juveniles was carried out under two temperature regimes: 32 a) natural conditions, and b) 3 ºC above the natural temperature (an increase predicted 33 for the NW Mediterranean by the end of this century). Fipronil was added to the fish 34 food (10 mg fipronil /Kg feed) and the effects were studied at several time points 35 including right before administration, 7 and 14 days after daily fipronil feed and one-36 week after the insecticide withdrawal from the diet (depuration period). A wide array of 37 physiological and metabolic biomarkers including feeding rate, general condition 38 indices, plasma and epidermal mucus metabolites, immune response, osmoregulation, 39 detoxification and oxidative-stress markers and digestive enzymes were assessed. 40 General linear models and principal component analyses indicated that regardless of 41 water temperature, fipronil resulted in a significant alteration of several of the above 42 listed biomarkers. Among them, glucose and lactate levels increased in plasma and 43 decreased in epidermal mucus as indicators of a stress response. Similarly, a depletion 44 in catalase activity and higher lipid peroxidation in liver of fipronil-exposed fish were 45 also indicative of an oxidative-stress condition. Fipronil induced a time dependent 46 inhibition of Cytochrome P450-related activities and an inhibition of phase II 47 glutathione-S-transferase. Moreover, fipronil administration was able to reduce the 48 hypo-osmoregulatory capability as shown by the increase of plasmatic osmolality and 49 altered several digestive enzymes including trypsin, lipase, alpha amylase and maltase. 50 Finally, analyses in bile and muscle confirmed the rapid clearance of fipronil but the 51 persistence of the metabolite fipronil-sulfone in bile even after the 7-day depuration 3 52 period. Altogether, the results reveal a notable impact of this compound on the 53 physiological condition of the European sea bass. The results should be considered in 54 future environmental risk assessment studies since fipronil could be hazardous to fish 55 species, particularly those inhabiting estuarine ecosystems exposed to the discharge of 56 agriculture runoffs where this pesticide is mainly used.