In recent years, an overwhelming amount of evidence has positively recommended a significant role of microbiota in human health and disease. Microbiota also plays a crucial role in the initiation, preparation, and function of the host immune response. Recently, it has been shown that short-chain fatty acids (SCFAs) are the primary metabolites of the intestinal microbiota produced by anaerobic fermentation, which contributes to the host-pathogen interaction. SCFAs, such as propionate, acetate, and butyrate, are bacterial metabolites with immunomodulatory activity, and they are indispensable for the maintenance of homeostasis. Some evidence indicates that they are involved in the development of infections. In the present study, we provide the latest findings on the role of SCFAs in response to bacterial infections.