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Background There was a fluctuation in medication demand and supply during COVID-19 pandemic. This study aimed to assess the trend of drug utilisation in Malaysia in 2018–2022 and evaluate the impact of COVID-19 on drug utilisation rates.Methods We conducted a repeated cross-sectional study of pharmaceutical sales data from public and private sectors in Malaysia from 2018 to 2022. Drug utilisation rates for the period after the onset of COVID-19 (2020–2022) was compared with the earlier period (2018–2019). Interrupted time-series regression analyses evaluated level and slope changes compared to pre-COVID-19 pandemic level for quarterly rates of drugs utilisation in public and private sectors.Results There was an immediate reduction in the utilisation rates for all drugs after COVID-19 in public (−20.4%; p = 0.043) and private sectors (−22.4%; p = 0.003). In both sectors, significant level changes were observed for anti-infectives, musculoskeletal, neurological, respiratory, and sensory organs preparations following COVID-19 pandemic, followed by a sustained increase in trend from 2020 to 2022. Public sector had a 22.2% reduction in the utilisation of cardiovascular drugs (p = 0.002), particularly for renin–angiotensin system (RAS) agents (−47.4%, p = 0.019). Private sector had large changes for anti-infectives (−53.6%, p