Background There were relatively few studies about the incidence and risk factors for bloodstream infection (BSI) in patients with severe acute respiratory distress syndrome (ARDS) supported by veno-venous extracorporeal membrane oxygenation (VV-ECMO). Methods Patients who were diagnosed with severe ARDS and received VV-ECMO treatment in the medical intensive care unit of China-Japan Friendship Hospital from August 2013 to March 2019 were retrospectively studied. The pathogens isolated from blood culture (BC) were identified and analyzed for drug sensitivity. The risk factors for BSI were analyzed by logistic regression. Results A total of 105 patients were included in this single-center retrospective cohort study. Among them, 23 patients (22%) had BSIs. 19 cases were identified as primary BSI; while the other 4 cases were as secondary BSI. A total of 23 pathogenic strains were isolated from BCs, including gram-negative (G(-)) bacilli in 21 (91%) cases, gram-positive (G(+)) cocci in 1 case, fungus in 1 case, and multidrug-resistant (MDR) organisms in 8 cases. Compared with patients without BSI, patients with BSI had a higher Murray score (odds ratio = 6.29, P = 0.01) and more blood transfusion (odds ratio = 1.27, P = 0.03) during ECMO. Conclusions The incidence of BSI in patients with severe ARDS supported by VV-ECMO was 22%. G(-) bacilli was the main pathogen, and most of them were MDR-G(-) bacilli (MDR-GNB). Higher Murray score and more blood transfusion may be the independent risk factors for BSI.