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The COVID-19 pandemic has resulted in a dramatic change in the delivery of primary healthcare across the world, presumably changing trends in consultations for infectious diseases and antibiotic use. This study aimed at describing and evaluating the impact of COVID-19 on antibiotic use in public primary care clinics in Malaysia between 2018 and 2021. Data from the nationwide procurement database of systemic antibiotics from public primary care clinics in Malaysia between January 2018 and December 2021 were analysed using interrupted time series analysis. The monthly number of defined daily doses per 1000 inhabitants per day (DID) was calculated and grouped by antibiotic class. The trend of antibiotic utilisation rates had been decreasing by 0.007 DID monthly before March 2020 (p = 0.659). With the introduction of national lockdown due to COVID-19 beginning March 2020, there was a significant reduction in the level of antibiotic utilisation rates of 0.707 (p = 0.022). Subsequently, the monthly trend showed a slight upward change until the end of the study period (p = 0.583). Our findings indicate that there was a significant decrease in antibiotic utilisation for systemic use in primary care following the COVID-19 pandemic compared with the preceding years (January 2018–March 2020).