Objective To analyze whether coronavirus disease 2019 (COVID-19) is a potential risk for the infection/colonization with multidrug-resistant organisms (MDROs) in hospitalized patients during a surge admission of COVID-19 patients. Methods Data of hospitalized patients in a tertiary first-class hospital from December 1, 2022 to January 31, 2023 were retrospectively analyzed. Clinical data, antimicrobial therapy, and MDROs detection result between COVID-19 patients and non-COVID-19 patients were compared. Patients with detected pathogens were divided into MDRO group and non-MDRO group. Risk factors for infection/colonization with MDROs in hospitalized patients were analyzed by multivariate logistic regression. Results A total of 16 710 patients were admitted in hospital, 2 403 cases were in COVID-19 group, and 8.83% (113/1 280) were MDRO-infected cases; 14 307 cases were in non-COVID-19 group, and 4.43% (167/3 770) were MDRO-infected cases. The detection rate of carbapenem-resistant Klebsiella pneumoniae (CRKP) in patients in COVID-19 group was higher than that in non-COVID-19 group (48.15% vs 30.89%, P=0.028). Multivariate analysis Results showed that critical illness (OR=4.796, 95%CI: 3.524-6.527), antimicrobial therapy ≥2 days before pathogen culture (OR=2.330, 95%CI: 1.699-3.196), positive fungi culture (OR=1.780, 95%CI: 1.318-2.405), long hospital stay (OR=1.036, 95%CI: 1.030-1.042) were risk factors for MDRO infection/colonization in hospitalized patients (all P<0.05). Conclusion During mass admission of COVID-19 patients, MDROs infection/colonization is related to critical illness, antimicrobial use, positive fungi culture and long hospital stay, while COVID-19 infection is not a risk factor for MDROs infection/colonization.