Background: The COVID-19 pandemic poses novel challenges in antimicrobial consumption metrics and stewardship strategies. COVID-19 patients became the major cause of hospital admission during the first wave of the pandemic, often leading to an antimicrobial prescription upon admission or treatment for superinfections. The aim of this study was to understand how antimicrobial consumption was impacted at the beginning of the pandemic in a tertiary care hospital, a reference center for COVID-19. Materials and Methods: A retrospective before-and-after study was done. Descriptive statistics of discharges, patient-days, and antimicrobial use indicators (defined daily doses (DDD)/100 discharges, DDD/100 patient-days) for various groups were calculated for the first three months of the pandemic (March, April, and May 2020) as a quarterly value, and for each year in 2011-2019, and their annual percentage changes were used to estimate 95% confidence intervals. The indicators were compared to patient type (medical/surgical), type of admission (urgent/elective), and age groups using Spearman's correlation coefficient. Results: Statistically significant increases occurred in 2020 for total antibacterials, macrolides, cephalosporins, amoxicillin/clavulanic acid, carbapenems, meropenem, and third-generation cephalosporins, while a reduction was seen in cefazolin/cefoxitin. A correlation was found between antibacterial consumption and patient or admission type. In 2020, unlike in pre-pandemic years, there was a different impact in DDD/100 discharges and DDD/100 patient-days due to increased lengths-of-stay and longer antimicrobial therapy. Conclusions: The COVID-19 pandemic led to an increase in antimicrobial consumption with a different impact in DDD/100 discharges and DDD/100 patient-days. This highlights the need to use both indicators simultaneously to better understand the causes of antimicrobial consumption variation and improve the design of effective antimicrobial stewardship interventions.