Providing oxygen therapy safely and effectively requires health-care professionals that havernsufficient knowledge, the right attitude, and evidence-based practice. Clinical practice guidelinesrnsuggest that oxygen be prescribed the same as any other drug; however, oxygen is oftenrnadministered excessively, discriminately without any prescription. This predisposes patients tornhyperoxia and hypoxemia. So, oxygen therapy by emergency and ICU nurses has importantrnimplications for patient outcomes. The objective of the study is to assess Nurses Knowledge,rnAttitude, and Practice regarding oxygen therapy in ICU, Emergency wards, and associatedrnfactors at selected Public hospitals of Mekele Town Tigray, Ethiopia,2021. A facility-basedrndescriptive cross-sectional study design was conducted. 199 Nurses selected by systematicrnrandom sampling technique from February 03, 2021 until April 28, 2021 and met the criteriarnwere included. Data was entered and analyzed using statistical software SPSS for windows Vrn26.0. The ethical clearance was obtained from Addis Ababa University College of healthrnSciences School of Nursing and Midwifery. The result showed that most of the study subjectsrnwere in the age range of 21-50. The mean age was 30.7 Â± 4.4 years. 118(62.1%) were males.rn112(58.9%) of nursesâ€Ÿ have sufficient knowledge toward oxygen therapy whereas 128(67.4%)rnnurses have positive attitude toward oxygen therapy. In addition 108 (56.8%) had satisfactoryrnpractice towards oxygen therapy. The presence of written prescription, OT guideline, and recentrnuse of OT was significantly associated with nursesâ€Ÿ knowledge. Meanwhile professional training,rnrecent use of OT and nurses department was significantly associated with nurses attitude.rnFurthermore Age, sex, presence of adequate oxygen delivery system, periodic maintenance ofrnoxygen system and on-job training were found to be significantly associated with oxygen therapyrnpractices (p