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Our aim was to assess the blood physiology and antioxidant and immune responses of the olive flounder (Paralichthys olivaceus) following pH changes in the water. P. olivaceus (mean weight 95.7 ± 6.5 g and mean length 21.4 ± 1.3 cm) were exposed to the different pH levels (pH 5, 6, 7, 8, 9, and 10) for 2 weeks. Blood physiology parameters, such as the levels of hematocrit, magnesium, glucose, glutamic oxalate transaminase (GOT), glutamic pyruvate transaminase (GPT), and alkaline phosphatase (ALP) were significantly altered by low (acidic) pH or high (alkaline) pHs. With regard to antioxidant responses, the superoxide dismutase (SOD) and glutathione S-transferase (GST) activities in the liver were significantly altered by the pH changes, but there were no significant changes of these activities in the gill tissues. The immunoglobulin M levels increased significantly at pH 10 after 2 weeks. The results of this study suggest that pH changes (acidity: < pH 6, alkalinity:> pH 9) affect blood physiology, as well as antioxidant and immune responses in P. olivaceus.