Oxygen is a commonly used medication. Insufficient oxygen levels in the bloodstream can lead to cellular malfunctions, organ failure, and ultimately, death. Oxygen, much like any other pharmaceutical substance, can be beneficial in reducing mortality when administered correctly, but it can also have adverse effects when misused. The use of supplemental oxygen therapy (SOT) plays a crucial role in preserving the lives of numerous patients suffering from cardio-pulmonary issues, requiring the development of updated guidelines. Objective: To assess the knowledge level of nurses and to identify the associated factors regarding oxygen administration for critical ill patients. Methods: A descriptive cross sectional study carried out among nurses of Shalamar hospital, Lahore with a sample size of 82. A modified form of questionnaire was used to collect data. Statistical chi-square test was utilized to analyze the study findings. Results: This study found that there were 69.5% females and 30.5% were male. Most of them had age between 20 to 30 years. Regarding knowledge level almost 75.6% participants had good knowledge, 19.5% had moderate knowledge with a mean score of 11.37. Furthermore there was a signification association among knowledge level and experience, duration of administration and duration of prescription with p<0.05 while gender, age, qualification and working area were not directly associated with the knowledge level of nurses with p>0.05. Conclusions: Most of participants were female having age between 20 to 30 years. Most of the nurses had good and moderate knowledge regarding supplemental oxygen therapy (SOT). So it needs a continuing education to stay updated regarding new guidelines for oxygen administration.