jats:titleAbstract</jats:title>jats:sec jats:titleBackground</jats:title> jats:pThe study aimed to describe the epidemiology and outcomes of hospital-acquired bloodstream infections (HABSIs) between COVID-19 and non-COVID-19 critically ill patients. </jats:p> </jats:sec>jats:sec jats:titleMethods</jats:title> jats:pWe used data from the Eurobact II study, a prospective observational multicontinental cohort study on HABSI treated in ICU. For the current analysis, we selected centers that included both COVID-19 and non-COVID-19 critically ill patients. We performed descriptive statistics between COVID-19 and non-COVID-19 in terms of patients’ characteristics, source of infection and microorganism distribution. We studied the association between COVID-19 status and mortality using multivariable fragility Cox models. </jats:p> </jats:sec>jats:sec jats:titleResults</jats:title> jats:pA total of 53 centers from 19 countries over the 5 continents were eligible. Overall, 829 patients (median age 65 years [IQR 55; 74]; male, jats:italicn</jats:italic> = 538 [64.9%]) were treated for a HABSI. Included patients comprised 252 (30.4%) COVID-19 and 577 (69.6%) non-COVID-19 patients. The time interval between hospital admission and HABSI was similar between both groups. Respiratory sources (40.1 vs. 26.0%, jats:italicp</jats:italic> < 0.0001) and primary HABSI (25.4% vs. 17.2%, jats:italicp</jats:italic> = 0.006) were more frequent in COVID-19 patients. COVID-19 patients had more often enterococcal (20.5% vs. 9%) and jats:italicAcinetobacter</jats:italic> spp. (18.8% vs. 13.6%) HABSIs. Bacteremic COVID-19 patients had an increased mortality hazard ratio (HR) versus non-COVID-19 patients (HR 1.91, 95% CI 1.49–2.45). </jats:p> </jats:sec>jats:sec jats:titleConclusions</jats:title> jats:pWe showed that the epidemiology of HABSI differed between COVID-19 and non-COVID-19 patients. Enterococcal HABSI predominated in COVID-19 patients. COVID-19 patients with HABSI had elevated risk of mortality.</jats:p> jats:pjats:italicTrial registration</jats:italic> ClinicalTrials.org number <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="https://clinicaltrials.gov/ct2/show/NCT03937245">NCT03937245</jats:ext-link>. Registered 3 May 2019. </jats:p> </jats:sec>