The large yellow croaker (Larimichthys crocea) is the marine culture fish most affected by white spot disease, with the highest frequency of C. irritans outbreaks in China. After years of efforts from scholars at home and abroad, many research progresses have been made in C. irritans propagation, pathogen pathology and vaccine research and development, but there are fewer studies on the physiological, biochemical and immune indexes of L. crocea infected with C. irritans. In order to understand the changes in various physiological and immune indicators of L. crocea after C. irritans infection, in this study, we selected 300 experimental fish for artificial C. irritans infection experiments at the peak of hatching of C. irritans cyst. The experimental fish were randomly assigned to three experimental groups and one control group. Blood, liver, spleen, intestines, gills, head kidney, and skin tissues were collected at 0, 12, 24, 48, and 72 h after infection to monitor changes in serum cortisol and corticosterone levels, liver glutathione peroxidase (GSH-Px) activity, superoxide dismutase (SOD) activity and malondialdehyde (MDA) level. Transcription patterns of TNF-α, IL-8 and IL-1β in liver, spleen, intestine, gill, head kidney, and skin tissues were detected by quantitative real-time PCR experiments. During the 3 days after infection, the serum cortisol and corticosterone level increased significantly and gradually from 0 h to 72 h after C. irritans infection (P<0.05); the GSH-Px activity in the liver showed a highly significant decreasing trend (P<0.001); the SOD activity in the liver showed an overall upward trend except for a decrease at 48 h (P<0.001); the MDA level in the liver increased sharply within 12 h, and began to decrease after reaching the peak (P<0.05); the expression of TNF-α, IL-8 and IL-1β in various tissues were upregulated to varied degrees, with those in the gills, head kindey, liver, and skin being the most obvious, which indicated these organs may play important roles in the immune response against C. irritans. These results suggested that corticosteroid content and oxidative stress indexes significantly changed after C. irritans infection can reflect the degree of infection in L. crocea, facilitating the optimization of anti-parasite trait assessment. This study contributes to understanding the dynamic physiological, biochemical, and immune changes after C. irritans infection in L. crocea, offering insights for subsequent mechanistic analyses and breeding efforts.