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The SARS-CoV-2 pandemic caused an increase in intensive care unit (ICU) hospitalizations with a rise in morbidity and mortality; nevertheless, there is still little evidence on the impact of the pandemic on antibiotic resistance in ICUs. This is a retrospective, monocentric epidemiological study. The aim of the study was to describe and analyze the impact of the SARS-CoV-2 pandemic on ICU bacterial resistance patterns. All bacteria isolated from all patients admitted to the E.O. Galliera ICU from January 2018 to December 2022 were included. Antibiotic resistance (AR) profiles were evaluated. A total of 1021 microorganisms were identified, of which 221 (12.47%) had a resistance pattern (resistant organisms; ROs). In this time, there were 1679 patients with a total of 12,030 hospitalization days. The majority of microorganisms were Gram-negative (79.66% in 2018, 77.29% in 2019, 61.83% in 2020, 62.56% in 2021, and 60.75% in 2022), but an increase in Gram-positive microorganisms was observed (20.34 to 39.25% between 2018 and 2022). The prevalence of AR was 19.44% in 2018, 11.54% in 2019, 38.04% in 2020, 34.15% in 2021, and 39.29% in 2022 for Gram-positive microorganisms and 19.86% in 2018, 13.56% in 2019, 18.12% in 2020, 12.41% in 2021, and 12.31% in 2012 for Gram-negative microorganisms. The incidence of ROs showed a COVID-19-related increase in 2020-2021, followed by a lowering trend since 2021, and a new increase in 2022. Possible explanations are antibiotic overtreatment and a decrease in containment measures. An interesting finding was the cumulative lowering trend of carbapenem-resistant K. pneumoniae and P. aeruginosa , probably due to different patient features.