Disinfection and sterilization are the basic components of hospital infection control activities. Every day several invasive procedures are being performed in different health facilities. Improper sterilization or disinfection of devices is associated with increasing risk of nosocomial infection. Nurses play a critical role in reprocessing respiratory equipment by adhering to infection prevention and control measures. This study aimed to assess nurses' knowledge, performance, and attitude regarding respiratory instrument processing in Mansoura hospitals. Method: A cross section study design was used. Setting: The study was conducted at four governmental hospitals in Mansoura city. (Chest hospital, Mansoura university hospital, Talkha, and Mansoura general hospital). Sample size: the study was carried out on 50 nurses who are responsible for instrument processing. The researcher used four tools in this study. Tool I: Nurses' socio demographic and occupational characteristics self-administrated questionnaire. Tool II: self-administrated questionnaire to assess the nurses' knowledge about instrument processing process (cleaning, disinfection, inspection, packing, sterilization, transport, storage, use and infection control measure), Tool III: Rubric observational checklist of respiratory instrument processing performance, Tool IV: Self-administered scale to assess attitude of nursing staff about the management of respiratory instrument processing. Results: the current study indicates that 60%, 66 % of studied nurses have poor total score level of knowledge and improper performance respectively regarding respiratory instrument processing. Conclusion: The study concluded that, most of the studied nurses have poor total knowledge score level, improper performance regarding respiratory instrument processing and the mean of total positive attitude was 44.8 (5.1). Recommendation: design protocol for nursing staff about respiratory instrument processing in Mansoura hospitals.