Anguilla anguilla L. were caged for 8 and 48 h in harbor water of Aveiro Lagoon, Portugal. Respiratory burst activity (RBA) of peritoneal, head kidney, and gill phagocytes was measured. Lipid peroxidation (LPO) was estimated in gill, kidney, and liver. Liver ethoxyresorufin-O-deethylase (EROD) activity, cytochrome P450 (Cyt P450) content, and bile metabolites were assayed. Various antioxidant enzymes, viz., glutathione peroxidase, catalase, and glutathione S-transferase and nonenzymatic antioxidant, viz., total reduced glutathione were also studied. Harbor water xenobiotics induced a significant RBA increase in gill after 8 h; whereas in peritoneum and head kidney it increased after 48 h exposure. These responses were adversely associated with tissue-specific peroxidative damage since significant LPO increase was observed in gill (8 and 48 h), kidney (48 h), and liver (48 h). The tissue most affected was gill. Moreover, liver EROD activity, Cyt P450 content and bile metabolites remain unaltered after 8 h; in contrast, 48 h exposure showed significant EROD activity decrease and pyrene-type bile metabolites increase. Decreased EROD activity may be associated with concomitant liver damage, as increased LPO was observed after 48 h. Furthermore, the tissue-specific damage corresponded to the differences in the antioxidant potentials of the tissues, since the initial exposure period caused a significant increase in liver antioxidant activities, whereas gill and kidney showed a significant decrease, demonstrating that liver is highly adaptive to oxidative damage. However, at 48 h exposure gill, kidney, and liver showed a suppressive antioxidant effect, probably due to PAHs, since a significant induction at PAH-type bile metabolites has been seen. Our results demonstrate that phagocyte activation and associated peroxidative damage are concomitantly corroborated with enzymatic and nonenzymatic antioxidant activity differences. In addition, hepatic antioxidant induction after short-term exposure may serve as a potent biomarker for water pollutants in fish.