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The study objectives were to examine antibiotic consumption at Vila Central Hospital (VCH), Vanuatu between January 2018 and December 2021 and the influence of the COVID-19 pandemic on antibiotic consumption during this period. Data on antibiotic usage were obtained from the Pharmacy database. We used the WHO’s Anatomical Therapeutic Classification/Defined Daily Dose (ATC/DDD) index, VCH’s inpatient bed numbers and the hospital’s catchment population to calculate monthly antibiotic consumption. The results were expressed as DDDs per 100 bed days for inpatients (DBDs) and DDDs per 1000 inhabitants per day for outpatients (DIDs). Interrupted time series (ITS) was used to assess the influence of COVID-19 by comparing data before (January 2018 to January 2020) and during (February 2020 to December 2021) the pandemic. Ten antibiotics were examined. In total, 226 DBDs and 266 DBDs were consumed before and during COVID-19 by inpatients, respectively with mean monthly consumption being significantly greater during COVID-19 than before the pandemic (2.66 (p = 0.009, 95% CI 0.71; 4.61)). Whilst outpatients consumed 102 DIDs and 92 DIDs before and during the pandemic, respectively, the difference was not statistically significant. Findings also indicated that outpatients consumed a significantly lower quantity of Watch antibiotics during COVID-19 than before the pandemic (0.066 (p = 0.002, 95% CI 0.03; 0.11)). The immediate impact of COVID-19 caused a reduction in both inpatient and outpatient mean monthly consumption by approximately 5% and 16%, respectively, and this was followed by an approximate 1% monthly increase until the end of the study. By mid-2021, consumption had returned to pre-pandemic levels. Full article