question: BACKGROUND: Multiple organ dysfunction syndrome secondary to infection is the leading cause of death in burn patients. Bloodstream infection (BSI) and the prognosis of burn patients are negatively correlated. Metagenomic next-generation sequencing (mNGS) can detect many potential pathogens and may be more valuable for patients with severe burns. METHODS: We retrospectively explored the utility of mNGS in describing the clinical and microbial characteristics of severely burned patients with BSI. We compared mNGS with blood culture. RESULTS: Fourteen patients (127 blood samples) developed 71 episodes of BSIs with 102 unique causative pathogens. The median total body surface area was 93%. The overall 90-day mortality was 43%. In total, 17 (23.9%) episodes were polymicrobial, and 61 (86.1%) episodes originated from the wound. In total, 62/71 cases (87%) showed positive findings by mNGS, while 42/71 cases (59%) showed positive findings using blood culture. We found that mNGS outperformed culture, especially in terms of fungi (27% vs. 6%, p < 0.0001). CONCLUSIONS: The incidence of BSI and polymicrobial in patients with large-area severe burns is high. mNGS has potential value in the diagnosis of fungal infections and coinfections in such patients. In addition, mNGS may provide unique guidance for antibiotic therapy in complicated BSI.