Background: World Health Organization has documented the exaggerated use of broad-spectrum antibiotics during the COVID-19 pandemic raising warnings of increasing antimicrobial resistance. Aim: This is an observational cross-sectional comparative study that was done to describe the pattern of antibiotics resistance before and during the COVID-19 era to explain if this pattern is affected with using different antibiotics in COVID-19 era. Methods: Various clinical specimens from patients admitted in the urology, internal medicine, surgery inwards, intensive care unit and neonatal ICU in Suez Canal University Hospital in the pre-COVID-19 period (January 2019 to January 2020) and during COVID-19 pandemic (January 2020 to January 2021) were included. 627 patients,349 (55.6%) patients in the pre-COVID-19 era and 278 (44.4%) patients during the COVID-19 era. Results: Most samples were Gram-negative organisms (86%), while gram-positive represent 14% only. The most common Gram-negative isolates include Escherichia coli (E. coli) (30.9%). The most common Gram-positive is Staphylococcus species (11.8%). The study found a statistically significant increase in the resistance for cefazoline (p=0.002), nitrofurantoin (p=<0.001), aztreonam (p=<0.001) and tobramycin (p=<0.001) during the COVID-19 era compared with the pre-COVID-19 era. Among the Gram-negative pathogens, there is a significant increase in the resistance for ampicillin (p=0.023), ciprofloxacin (p=0.013), nitrofurantoin (p=<0.001), aztreonam (p=<0.001), tobramycin (p=0.035), trimethoprim -sulphamethoxazole  (p=0.029), cefazoline (p=0.011), aztreonam (p<0.001), tigecyclin (p=0.048), and amikacin (p=0.043) during the COVID-19 compared with before, but the susceptibility pattern for the Gram-positive pathogens did not vary in both periods. Conclusion: COVID-19 pandemic led to the uncontrolled use of broad-spectrum antimicrobials, causing an increase in the antimicrobials resistance (AMR). Strict adherence to antimicrobial stewardship is essential.