Oxygen therapy is one of the main interventions that is used to manage the respiratory abnormalities. Oxygen therapy is a basic requirement prescribed largely for hypoxic patients. It depending on the basic medical condition of a patient, and whether the condition is acute or chronic, the best amount and method of oxygen delivery system. The uses of oxygen to those patients who have adverse events related to respiration, such as unexpected death, cardiac arrest, or accidental intensive care unit admissions. In this study it is important to check the knowledge and practices of nurses about the administration of oxygen on critical patients in ICU and medical and surgical ward and enhance their practices. A descriptive study design will be used in this research study.The study will be conducted in the different ICUs, CCU, Emergencies and medical and surgical wards, in Sheikh Zayed hospital Lahore. The population for this study is the nurses including graduated nurses, diploma holder nurses, nurses who have more than 1 year of experience. 133 is a sample size for this study. Random sampling technique used for this study. The likert scale questionnaire is used for knowledge assessment and observation tool is used to assess the practices of the nurses on a safe oxygen administration therapy. The mean score of knowledge is ±1.01, the practices before administration of oxygen mean score is ± 1.08, during oxygen administration mean score is ± 0.93, and after oxygen administration means score is ± 1.045. This study concluded that, a majority of the studied sample had satisfactory level of knowledge and had adequate level of practices.