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Black rockfish (Sebastes schlegelii) is a marine fish with high financial value; however, the frequent occurrence of bacterial diseases has caused a production decline and economic losses. This study found that hyperemia, hemorrhage, and ascites were common in S. schlegelii during the V. parahaemolyticus infection. Inflammation, degeneration, and necrosis in the liver could be observed. The epithelial mucosal integrity, the intestine epidermis thickness, the villus heights, and the number of mucous cells in the intestine were decreased after infection. Apparent differences in most of the hematological parameters between the two groups were observed, such as the corpuscular volume (CV) and NaCl concentrations of the beginning hemolysis were decreased remarkably (P < 0.01) after infecting with V. parahaemolyticus. However, the white blood cell count (WBC), lysozyme (LZM), malondialdehyde (MDA), K+, Cl−, and Ca2+ were increased significantly (P < 0.01) after infection. In addition, the mRNA expressions in four tissues (gills, liver, blood, spleen) of eleven immune-related genes were investigated. The results showed that C1r, C1s, and C1inh expression varied considerably among tissues. Caspase 10 expression was reduced in four tissues after infection, but MyD88, TNF receptor, TNF-α, BAFF, IL-1β, IL-8, and IL-10 showed increased expression profiles within 24 h after infection. In particular, IL-1β expression in the liver and spleen increased 123.67 and 104.94-fold at 6 hpi, respectively. Therefore, in addition to pathology, the hematological detection and gene expression profiles could be used in the evaluation of healthy status in fish, and this study provided a preliminary basis for the diagnosis of S. schlegelii infecting with V. parahaemolyticus. [ABSTRACT FROM AUTHOR]