Sepsis syndrome is a common and frequently fatal clinical condition. It is defined by the presence of both infection and an uncontrolled systemic inflammatory response. It represents a major, although largely unappreciated, healthcare problem worldwide. It is especially problematic in infants and toddlers who show markedly increased susceptibility to severe infections caused by various pathogens, including viruses. Viruses are important causative agents of sepsis. Host adenosine deaminase acting on RNA 1 (ADAR1) catalyzes adenosine to inosine (A-to-I) editing of RNA transcripts, thus changing viral RNAs and exerting antiviral and proviral effects. In addition, ADAR1 promotes viral replication by directly interacting with protein kinase R and suppressing its kinase activity. We here discuss the function of ADAR1 and its regulatory role in viral infection. Further, we establish the relationship between ADAR1 and virus-associated sepsis, thus providing an important basis for the development of novel therapeutic targets for the treatment of virus-associated sepsis.