Schizothorax macropogon is a second-grade protected animal with high ecological and economic value. Currently, most of the related research has focused on resource investigation, individual biology, and population genetics. However, to date, there have been relatively few studies on gut microorganisms. In this study, we extracted the intestinal contents of S. macropogon with saprolegniasis and healthy states, respectively. We analyzed the number of OTUs, colony composition, abundance, and Alpha diversity of intestinal microorganisms, and predicted their functions by high-throughput sequencing. Alpha diversity analysis showed that the richness and diversity of the gut microbial community in the healthy group was higher than that in the sick group. PCoA analysis showed that there was a significant difference between the gut microbes in the healthy and sick group of S. macropogon. The histogram of species distribution showed that the gut microorganisms in the healthy group and sick group of S. macropogon were similar in the composition of community structure but differed in relative abundance. Bacteria acquired a total of seven dominant phyla, including Cyanobacteria, Proteobacteria, and Fusobacteriota. The endemic genera in the diseased group were Bacteroides, and Proteocatella. Five dominant phyla of fungus were obtained, including Ascomycota, Basidobolomycota, and Rozellomycota. The endemic genus in the healthy group was Cererhiza, and the endemic genera in the sick group were Boeremia and Tausonia The discriminant plot statistics showed that the healthy group had the highest number of fungi in the healthy group. The discriminant plot showed that there were 38 bacterial marker species and 45 fungal marker species between the healthy group and sick group in the gut of S. macropogon. The co-occurrence network of microorganisms in the intestine of S. macropogon had high connectivity and coherence. According to the functional prediction analysis, there was a significant difference in the functional flora of intestinal bacteria between the healthy group and the sick group (P＜0.05). The relative abundance of the healthy group was higher than that of the sick group. The present study revealed the community composition and diversity of the gut microorganisms of S. macropogon, preliminarily analyzed the relationship between the health status of S. macropogon, and its gut microorganisms, and provided a database for the study of the intestinal flora of endemic fishes in the Qinghai–Xizang Plateau.