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Salah H Elsafi,1 Saleh H Almutairi,2 Mujahid A Alsulaimani,3 Salma AlBahrani,4 Thekra N Al-Maqati,1 Wafa K Alanazi,2 Mohammed N Alanazi,2 Abdullah A Alamri,2 Majed Hamoud Alkhathami,5 Rakkad A Alshammari,5 Naif F Alharbi,5 Yaser A Al Naam1 1Clinical Laboratory Sciences. Prince Sultan Military College of Health Sciences, Dhahran, Saudia Arabia; 2Pharmacy Services Department, King Fahad Military Medical Complex, Dhahran, Saudi Arabia; 3Basic Medical Unit, Prince Sultan Military College of Health Sciences, Dhahran, Saudia Arabia; 4Infectious Disease Unit, Specialty Internal Medicine, King Fahhd Military Medical Complex, Dhahran Saudi Arabia; College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudia Arabia; 5Department of Support Services, Prince Sultan Military College of Health Sciences, Dhahran, Saudia ArabiaCorrespondence: Yaser A Al Naam, Prince Sultan Military College of Health Sciences, P. O Box 33048, Dammam, 31448, Saudia Arabia, Email yaser@psmchs.edu.saBackground: Earlier reports suggested high rates of antibiotic utilization among COVID-19 patients despite the lack of direct evidence of their activity against viral pathogens. Different trends in antibiotic consumption during 2020 compared to 2019 have been reported.Purpose: The objective of this study is to assess the impact of COVID-19 pandemic on antibiotic consumption in the presence of active Antibiotic Stewardship Program.Methods: This study represented a five years assessment of the consumption of the commonly prescribed antibiotics measured as DDDs/100-Bed Days. We analyzed the data by using nonparametric Friedman and Friedman tests to compare the antibiotic consumption before and during the three subsequent waves of COVID-19.Results: Antibiotic consumption through the DDDs/100-BD has shown reduction in the median of antibiotics consumption of most antibiotics during the period of COVID-19 as compared to the pre-COVID-19 period, which was significant for meropenem and ciprofloxacin, except colomycin that slightly increased. Significant reduction in the consumption of imipenem and meropenem during the second and third waves as compared to the pre-COVID period. Throughout the years, significant reductions were observed between 2018 and 2019 (p=< .001), 2018 and 2020 (p=0.008), and 2018 and 2022 (p=0.002).Conclusion: The reduction in antibiotic consumption is attributed to the strong influence if the ASP and the reluctance of people to visit hospitals during the COVID-19 pandemic. Other related COVID-19 precautions such as physical distance, good hand hygiene, facemasks, that resulted in the prevention of secondary bacterial infections have contributed to the reduction in antibiotic utilization during the pandemic.Keywords: antimicrobial stewardship, ASP, COVID-19, defined daily doses, DDD, antibiotic consumption, Saudi Arabia