Nitrite is a common pollutant in aquaculture water, and nitrite toxicity that negatively affects aquatic species is common in aquaculture systems when the water quality is low. Therefore, the present research aimed to evaluate the effect of acute nitrite exposure on the hematological parameters, antioxidant enzymes, immune response, and gill morphology of large yellow croaker ( Larimichthys crocea ). The fish were randomly separated and exposed to four (i.e., 0, 29.36, 58.73, and 88.09 mg/L) nitrite concentrations for 48 h. The fish blood and gills were collected at 0, 12, 24, 36, and 48 h of nitrite exposure for further analysis. In hematological parameters, the results showed that the levels of hemoglobin, triglyceride, and total cholesterol in blood significantly decreased ( p < 0.05) in all nitrite-treated samples after 12 h, while the contents of methemoglobin in blood significantly increased ( p < 0.05) in these treatments. After 48 h of nitrite exposure, the levels of cortisol in serum showed a 94.5%, 132.1%, and 165.6% increase in fish exposed to 29.36, 58.73, and 88.09 mg/L nitrite, respectively. The nitrite (i.e., 29.36, 58.73, and 88.09 mg/L) exposure significantly increased ( p < 0.05) the levels of antioxidant enzymes (i.e., catalase and glutathione) in the gill and serum after 12 h of exposure compared with the control. The lysozyme levels in serum decreased in the nitrite (i.e., 29.36, 58.73, and 88.09 mg/L) exposure samples. It was found that immunoglobulin levels in the 29.36, 58.73, and 88.09 mg/L nitrite-treated samples (i.e., 1.86, 1.58, and 0.74 μg/mL, respectively) were lower than that of the control (2.56 μg/mL). In addition, the surface of the gill lamellae displayed deformation and contraction after 48 h of nitrite, especially in the fish exposed to 88.09 mg/L nitrite. These results indicate that the nitrite exposure induced the oxidative stress, affected the immune response, and changed the gill morphology, leading to nitrite poisoning in large yellow croaker.