BACKGROUND: The COVID-19 pandemic led to major disruptions in health-care services at the hospital and community levels, with uncertain consequences on antibiotic resistance in hospitals. Here, we quantify changes of antibiotic resistance incidence during the COVID-19 pandemic in France. METHODS: We extracted data from the French national surveillance system on antibiotic resistance and antibiotic use in hospitals between 2019 and 2022. Included were 692 551 incident isolates for five antibiotic-bacterium pairs isolated from 414 hospitals across 12 French regions. First, we evaluated changes in annual antibiotic use in 2020-22 compared with 2019. Then, we evaluated associations between resistant isolates incidence and COVID-19 indicators (pandemic periods or prevalence of patients with COVID-19) using negative binomial regression models accounting for autocorrelation and antibiotic use. Associations were assessed at the national level, in intensive care units (ICUs; n=85), and across geographical regions. FINDINGS: The use of some antibiotics, including azithromycin, imipenem, and meropenem, significantly increased over the 2020-22 period compared with 2019. Concomitantly, the incidence of methicillin-resistant Staphylococcus aureus (up to 37% [95% CI 18-53]) and extended-spectrum β-lactamase (ESBL)-producing Escherichia coli (up to 33% [16-46]) isolates significantly decreased during COVID-19 pandemic years in hospitals and ICUs. ESBL-producing Klebsiella pneumoniae showed a transient significant decrease in ICUs during periods of strong anti-COVID-19 interventions in the community (24% [6-39]), whereas no signal was found for ESBL-producing Enterobacter cloacae complex. Importantly, the incidence of carbapenem-resistant Pseudomonas aeruginosa isolates was associated with COVID-19 prevalence in hospitals (p<0⸱0001) and ICUs (p=0⸱0002), notably in the regions most affected by the pandemic. INTERPRETATION: Our results highlight alterations in antibiotic use and pathogen-specific effects of the pandemic on antibiotic resistance in hospitals. Although the biological mechanisms underlying between-species differences remain unclear, these results provide insights into the potential effects of a viral pandemic on antibiotic resistance and support the need for pandemic preparedness in health-care facilities. FUNDING: l'Agence nationale de la recherche Labex Integrative Biology of Emerging Infectious Diseases.