This study aimed to evaluate the cleaning practices of non-critical medical equipment (NCME) among nurses working at Debre Tabor Comprehensive Specialized Hospital (DTCSH) in north-central Ethiopia during the COVID-19 pandemic. A facility-based cross-sectional study was carried out at Debre Tabor Comprehensive Specialized Hospital (DTCSH), Ethiopia, from July 5 to August 5, 2020. The study was conducted in inpatient and outpatient units of the hospital. The study involved observations of 76 randomly chosen staff nurses, alongside interviews with 6 head nurses.” Only 1.3% to 5.3% of nurses cleaned stethoscopes, thermometers, pulse oximeters, and glucometers immediately after patient use. None of the nurses reported cleaning blood pressure devices before or after measuring a patient’s blood pressure, nor glucometers prior to assessing blood glucose levels. Head nurses identified the primary barriers to proper cleaning practices as a shortage of disinfecting materials and insufficient training on infection prevention. The cleaning practices of non-critical medical equipment (NCME) among nurses were found to be very low. Therefore, ensuring an adequate supply of cleaning materials is essential, along with providing nurses with targeted training on infection prevention.