Background: Antimicrobial resistance is a rising threat worldwide; this problem has been exacerbated especially after emergence of COVID-19 pandemic. The purpose of this work was to describe the change in the prevalence rate and resistance pattern of respiratory targeting pathogens during COVID-19 pandemic compared to the era before Methods: A cross-sectional study included retrospective part (before COVID-19) and prospective one (during COVID-19) was conducted on ICU patients in Jizan Armed Forces Hospital. Respiratory and blood samples were obtained. VITEK II compact system (bioMerieux, UK) was used to identify bacterial isolates and their antimicrobial sensitivity pattern. Results: Gram-negative bacteria were predominant in both periods, although their proportion slightly decreased during COVID. Conversely, Gram-positive bacteria increased. MDR organisms increased significantly by 12.1% while XDR organisms also showed an increase by 2.3%. The prevalence of E. coli, Klebsiella pneumoniae has been increased (p = 0.044, p < 0.001, respectively), while Pseudomonas aeruginosa, Acinetobacter baumannii and Proteus Mirabilis decreased (p = 0.003, p<0.001and p=0.021, respectively). The prevalence of Staphylococcus aureus and Staphylococcus epidermidis showed no statistically significant difference. For Pseudomonas aeruginosa, there was a decrease in sensitivity to gentamicin, ceftazidime, imipenem and piperacillin/tazobactam. Also, a decrease in sensitivity to gentamicin, levofloxacin, cefoxitin, ciprofloxacin, and piperacillin/tazobactam has been encountered with E. coli and klebsiella. Staph. aureus showed a decrease in sensitivity to ciprofloxacin, clindamycin, azythromycin, gentamicin, and moxifloxacin during COVID. Conclusion: Changing the prevalence of bacteria and rising level of their resistance to several antibiotics are critical issues that have emerged during COVID pandemic.