Abstract: 【Objective】 To investigate the effects of high-level replacement of fish meal with Clostridium autoethanogenum protein（CAP） and curcumin（CUR） supplement on the growth, immunity and intestinal health of Litopenaeus vannamei, which could provide research basis for the rational application of CUR and CAP in the feed of Litopenaeus vannamei. 【Method】 A total of 480 healthy juvenile Litopenaeus vannamei of uniform size were selected and randomly divided into 4 groups, which were fed basal feed（FM group）, low fish meal feed with 70% fish meal replaced by CAP（LFM group）, low fish meal diet supplemented with 0.006% CUR（LC1 group）, and low fish meal diet supplemented with 0.012% CUR（LC2 group） respectively. After 8 weeks of culture, the growth performance, serum biochemical indexes and intestinal digestive enzyme activities of Litopenaeus vannamei in each treatment group were measured, intestinal morphology was observed, and the composition of intestinal microbiota was analyzed. 【Result】 Compared with FM group, the final body weight, weight gain rate and specific growth rate of Litopenaeus vannamei in LFM group decreased significantly（P＜0.05, the same below）, and the feed coefficient rate increased significantly. Compared with the LFM group, Litopenaeus vannamei in the LC1 and LC2 groups exhibited significantly increased final body weight, weight gain rate and specific growth rate, along with a significantly decreased feed coefficient rate; moreover, except feed coefficient rate, the LC1 group demonstrated better overall growth performance indexes than the LC2 group. The activities of superoxide dismutase（SOD） and catalase（CAT） in serum as well as amylase and protease in the intestine of Litopenaeus vannamei in the LFM group were significantly lower than those in the FM group, whereas malondialdehyde（MDA） content and lysozyme（LYS） activity in serum were significantly higher than those in the FM group. Compared with the LFM group, the MDA content in LC1 group and LC2 group was significantly decreased, and the activities of SOD and CAT were significantly increased. The protease and amylase activities in LC1 group were significantly higher than those in LFM group. Observation of intestinal sections showed that the intestinal villus folds in the LFM group tended to be flat and disappeared, and some epithelial cells fell off. The epithelial cell height was greatly lower than those in the FM group. The intestinal morphology of the LC1 group and the LC2 group was greatly improved compared with the LFM group. The results of Alpha diversity analysis showed that the ACE and Chao1 indexes of intestinal microbiota in LC1 group were higher than those in FM group and LFM group. Compared with the LFM group, the LC1 group showed significantly decreased relative abundance of Proteobacteria and Cyanobacteria, but significantly increased relative abundance of Bacteroidota and Actinobacteriota in the intestinal microbiota. Additionally, the relative abundance of Ruegeria increased, while that of Vibrio decreased significantly. 【Conclusion】 Replacement of fish meal with CAP can cause a decrease in the growth performance of Litopenaeus vannamei, and affect the body’s immunity and intestinal health. Adding an appropriate amount of CUR can enhance the diversity of the intestinal flora of Litopenaeus vannamei, increase beneficial bacteria and reduce harmful ones, effectively alleviate intestinal damage caused by high-level replacement of CAP, improve intestinal health, and thereby enhance the immune capacity and growth performance of Litopenaeus vannamei.