Abstract: To investigate the drug accumulation-elimination kinetics in tissues and hepatic detoxification response of juvenile black porgy (Acanthopagrus schlegelii) after enrofloxacin bath immersion, we subjected the juveniles to a 24-hour bath administration with enrofloxacin at concentrations of 5 and 10 mg·L⁻¹, and determined the drug residues in the liver, gills, and muscle, as well as the hepatic biochemical indices within 7 d of depuration. The results revealed distinct dose-dependent and organ-specific accumulation of enrofloxacin in the juveniles. The liver was identified as the primary accumulation organ, exhibiting the highest residue levels, area under the curve (AUC_0-t), and mean residence time (MRT). Critically, the elimination half-life of enrofloxacin in muscle was longer than that in liver and gill tissues, suggesting that muscle is a long-term risk organ for drug residues. Enrofloxacin bath administration disrupted the hepatic detoxification system by markedly suppressing cytochrome P450 (CYP450) contents and elevating glutathione S-transferase (GST) activities. Enrofloxacin administration further disrupted the hepatic antioxidant defense system, evinced by sustained inhibition of superoxide dismutase (SOD) activities and significant up-regulation of catalase (CAT) activities and malondialdehyde (MDA) contents. The integrated biomarker response (IBRv2) index showed that the toxicity of enrofloxacin exhibited a significant dose-dependent effect, and a relatively high integrated toxic load was still observed even after 7 d of depuration. Although the enrofloxacin residues in various tissues of juvenile fish could decrease to below the maximum residue limit (MRL) of 100 μg·kg⁻¹ within 48–72 h, the disorder of detoxification metabolism and oxidative damage in the liver could persist for more than 7 d. The study indicates that the accumulation and elimination of enrofloxacin residues in juvenile A. schlegelii after bath administration were tissue-specific, and the recovery of liver physiological functions lagged significantly behind the elimination of drug residues.