Background : COPD is a progressive, respiratory disease characterised by persistent airflow limitation due to damage caused by significant exposure to noxious particles or gases . Nurses play an important role to care COPD patients. The nurse should have knowledge of basic principles, indications, application methods, complications of oxygen therapy, appropriate oxygen therapy can save lives. Aim : this study aimed to assess nurses' knowledge and practice regarding oxygen therapy for patients with COPD. Research design : An descriptive research design was adopted. Setting : The current study was conducted at Chest Department and ICU Chest at Beni-Suef University Hospital and Chest Hospital at Beni –Suef Governorate . Subject : Convenience sample (114 ) of all available staff nurses, who are working in the previously mentioned settings . Tool for data collection : two tools were used to collection of data; nurses self –administered questionnaire and nurses' Observation checklist. Result : The study revealed that (65.8%) of the studied nurses were aged between 20 and 30 years and (59.6%) of the studied nurses had technical nursing institute. About (65.8%) of the studied nurses had unsatisfactory levels of knowledge and ( 85.1%) of the studied nurses had incompetent level of practice regarding oxygen therapy . Conclusion: The majority of studied nurses had an unsatisfactory level of knowledge and incomplete level of practices regarding oxygen therapy for patients with COPD. Recommendation : Implementation of educational programs