The identification of novel serum biomarkers holds great value for diagnosing and monitoring disease conditions due to its convenient and non-invasive nature. Recently, great interests have been shed on serum microRNAs (miRNAs), which emerge as promising biomarkers for a variety of diseases including cancer and metabolic disorders (Cortez et al., 2011). Despite the concentrated attention on serum miRNAs, the reports on the existence and diagnostic value of other serum small RNAs remain surprisingly few. In present study, we identify and characterize an ancient class of tRNA-derived small RNAs (tsRNAs) that abundantly and conservatively exist across a wide range of vertebrate species (from fish to human) and demonstrate their sensitive response to body infection in mouse, monkey, and human being.