To analyze the distribution and drug resistance change of Klebsiella pneumoniae (KP) isolates from the patients hospitalized in the department of respiratory and critical care medicine before and after COVID-19 Pandemic, and provide references for further proper use of antibiotics. Methods Data of pathogens in the year pre COVID-19 Pandemic (Jan to Dec, 2019) and post Pandemic year (May 2020 to Mar 2021) were collected by the WHONET 5. 6 software. The source of specimens, detection rate of KP, detection rate drug resistant KP, and drug resistance profiles were compared. Results Specimens used for microbiological examination were mainly sputum and bronchoalveolar lavage fluids. The detection rate of KP isolates from the post Pandemic year was significantly higher than those from pre-Pandemic year (P＜0.05). Drug resistant KP had higher resistance rates to aztreonam (26.39%), ceftazidime (26.39%), cefotaxime (25.46%), piperacillin/tazobactam (24.54%), and compound sulfamethoxazole (18.06%) in the pre-Pandemic year, and to cefotaxime (29.78%), aztreonam (29.21%), piperacillin/tazobactam (25.84%), ciprofloxacin (16.29%) and ertapenem (16.29%). Compared to the pre-Pandemic year, resistance rates of KP against compound sulfamethoxazole decreased significantly in the post Pandemic year (P＜0.05). No significantly change was observed in resistance rates of ESBL-KP (P＜0.05). Conclusion COVID-19 Pandemic has remarkably influenced the isolation rate of KP. It is suggested that precise and active intervention measures should be taken to prevent the emergence and prevalence of drug resistant KP in the period of COVID-19 epidemic.