Derived from polycyclic aromatic hydrocarbons (PAHs), oxygenated-PAHs (oxy-PAHs) may pose hazards to aquatic organisms, which remains largely unknown. Takifugu obscurus is an important anadromous fish species of high economic and ecological values. In the present study, T. obscurus was acutely exposed to 44.29 μg/L 9,10-phenanthrenequione (9,10-PQ) for 96 hours. Changes of antioxidant indices and metabolite profiles in plasma were compared between 9,10-PQ treatment and the control. The results showed that 9,10-PQ treatment significantly increased MDA content during 6 hours to 96 hours, increased SOD and CAT activities at 6 hours, but decreased them at 96 hours. These results indicated that 9,10-PQ induced oxidative stress to fish. Ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) analysis revealed that four metabolic pathways were influenced in response to treatment with 9,10-PQ, including glycerophospholipid metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, purine metabolism and sulfur metabolism. These pathways are associated with antioxidant mechanisms, biosynthesis of neurotransmitters and innate immune functions. Thus, the as-obtained results confirmed that 9,10-PQ induced oxidative stress and raised concerns of neurotoxicity and immunotoxicity to fish. Overall, the present study posed a high environmental risk of oxy-PAHs to aquatic ecosystems. Derived from polycyclic aromatic hydrocarbons (PAHs), oxygenated-PAHs (oxy-PAHs) may pose hazards to aquatic organisms, which remains largely unknown. Takifugu obscurus is an important anadromous fish species of high economic and ecological values. In the present study, T. obscurus was acutely exposed to 44.29 μg/L 9,10-phenanthrenequione (9,10-PQ) for 96 hours. Changes of antioxidant indices and metabolite profiles in plasma were compared between 9,10-PQ treatment and the control. The results showed that 9,10-PQ treatment significantly increased MDA content during 6 hours to 96 hours, increased SOD and CAT activities at 6 hours, but decreased them at 96 hours. These results indicated that 9,10-PQ induced oxidative stress to fish. Ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) analysis revealed that four metabolic pathways were influenced in response to treatment with 9,10-PQ, including glycerophospholipid metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, purine metabolism and sulfur metabolism. These pathways are associated with antioxidant mechanisms, biosynthesis of neurotransmitters and innate immune functions. Thus, the as-obtained results confirmed that 9,10-PQ induced oxidative stress and raised concerns of neurotoxicity and immunotoxicity to fish. Overall, the present study posed a high environmental risk of oxy-PAHs to aquatic ecosystems.