Bloodstream infections are featured by acute onset, rapid progression and high mortality. Early identification and accurate prognostic assessment are crucial for improving patient outcomes. This article reviews five novel biomarkers in assessing the severity and prognosis of patients with acute bloodstream infection, namely soluble triggering receptor expressed on myeloid cell-1, soluble form of the urokinase plasminogen activator receptor, presepsin, heparin-binding protein and microRNAs, all of which are positively correlated with the severity of patients’ condition, and some perform better than traditional biomarkers. However, they still have limitations such as inadequate specificity or sensitivity and lack of large-scale verification. In the future, it is necessary to integrate molecular detection and artificial intelligence to optimize application strategies and provide personalized diagnosis and treatment.