Purpose Patients presenting the most severe form of coronavirus disease 2019 (COVID-19) pneumonia, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), have a prolonged intensive care unit (ICU) stay and are exposed to broad-spectrum antibiotics, but the impact of COVID-19 on antimicrobial resistance is unknown. Methods Observational prospective before-after study in 7 ICUs in France. All consecutive patients with an ICU stay > 48 h and a confirmed SARS-CoV-2 infection were included prospectively and followed for 28 days. Patients underwent systematic screening for colonization with multidrug-resistant (MDR) bacteria upon admission and every week subsequently. COVID-19 patients were compared to a recent prospective cohort of control patients from the same ICUs. The primary objective was to investigate the association of COVID-19 with the cumulative incidence of a composite outcome including ICU-acquired colonization and/or infection related to MDR bacteria (ICU-MDR-col and ICU-MDR-inf, respectively). Results From February 27th, 2020 to June 2nd, 2021, 367 COVID-19 patients were included, and compared to 680 controls. After adjustment for prespecified baseline confounders, the cumulative incidence of ICU-MDR-col and/or ICU-MDR-inf was not significantly different between groups (adjusted sub-hazard ratio [sHR] 1.39, 95% confidence interval [CI] 0.91–2.09). When considering both outcomes separately, COVID-19 patients had a higher incidence of ICU-MDR-inf than controls (adjusted sHR 2.50, 95% CI 1.90–3.28), but the incidence of ICU-MDR-col was not significantly different between groups (adjusted sHR 1.27, 95% CI 0.85–1.88). Conclusion COVID-19 patients had an increased incidence of ICU-MDR-inf compared to controls, but the difference was not significant when considering a composite outcome including ICU-MDR-col and/or ICU-MDR-inf.