Pacific oysters (Crassostrea gigas) are widely cultured in Chinese marine ranching with high economic value. However, mass death of farmed oysters has occurred frequently in recent years because of diseases and environmental disturbance (e.g., high temperatures). In order to analyze the potential relationships between microorganisms and the death of farmed oysters, we compared the dynamics of bacterial and protist communities in oysters at different growth phases using high-throughput sequencing. The results showed that the microbial communities in farmed oysters significantly changed and were markedly different from microbes in natural oysters and the surrounding environments. The number of biomarker taxa among farmed oysters and their surrounding environments decreased gradually with the growth of oysters. During the mass death of farmed oysters, the microbial communities’ abundance of ecological function genes changed, and the correlations among microorganisms disappeared. These results enrich our understanding of the dynamics of microbial communities in farmed oysters at different growth phases, illustrating the characteristics of interactions among microorganisms during the mass death of farmed oysters. Our study is beneficial to promote the healthy aquaculture of oysters.