The study aimed to comprehensively describe and evaluate the pathogenic and clinical characteristics of severe fever with thrombocytopenia syndrome (SFTS) patients with co-infections.We retrospectively collected clinical data and laboratory indicators of the SFTS patients at Tongji Hospital from October 2021 to July 2023.A total of 157 patients with SFTS virus (SFTSV) infection were involved in the analysis, including 43 co-infection and 114 non-co-infection patients. The pathogens responsible for co-infection were primarily isolated from respiratory specimens. Fungal infections, primarily Aspergillus fumigatus, were observed in 22 cases. Bacterial infections, with Klebsiella pneumoniae and carbapenem-resistant Acinetobacter baumannii as the main pathogens, were identified in 20 cases. SFTS patients with co-infection exhibited higher mortality (P=0.011) compared to non-co-infection patients. Among SFTS patients co-infected with both bacteria and fungi (8 cases) or specific drug-resistant strains (11 cases), the mortality rate was as high as 70% (14/19). In comparison with the non-co-infection group, SFTS patients with co-infection displayed significant alteration in inflammatory markers, coagulation function, and liver function indicators.The mortality rate of SFTS patients with co-infection is relatively high, underscoring the need for enhanced monitoring and timely, appropriate treatment to minimize the mortality rate.Copyright © 2023 Song, Zou, Huang, Wang, Wang, Wei, Sun and Hou.