Clostridioides difficile infection (CDI) causes the greatest number of healthcare-associated infectious diarrhoea. CDIs are transmitted by direct and indirect patient-to-patient contact and risk increases with the use of antibiotics. Since early 2020, the COVID-19 pandemic has affected healthcare systems in many ways including substantial changes in hygiene behaviour. The aim of this study was to assess whether CDI incidence differed during the COVID-19 pandemic compared to a year before. All tests for suspected CDI cases were recorded for a hospital in Brussels, Belgium. The percentage of CDI-positive results and incidences (total and healthcare-associated (HA)-CDI)) for years 2019, 2020, 2021, and 2022 were calculated. Antibiotic consumption was analysed for years 2019 and 2020. Since the COVID-19 pandemic struck, a significant reduction of up to 39% was observed in the number of Clostridioides difficile stool tests in our hospital. A significant decrease in the percentage of positive tests and a 50% ...