BACKGROUND: Operating room nurses (ORNs) who directly deal with the treatment and care of COVID-19 patients during the pandemic are at risk in terms of psychological stress and other mental health problems. OBJECTIVE: The aim of the study was to compare the anxiety and depression levels of ORNs working in different countries in the COVID-19 outbreak, and to determine the predictors and the difference between countries. METHODS: This was a descriptive and cross-sectional study. Data were collected online using a google form between February 2021-February 2022. The universe of the research is nurses who are members of national Perioperative Nurses Association (USA, Türkiye, Australia, England, India, Israel) and 1127 ORNs participated the study. In multivariate analysis, independent predictors of anxiety and depression status were examined by binary logistic regression analysis. RESULTS: The rate of anxiety is 5.46 times higher in nurses in the USA, 5.07 times higher among nurses in Australia, and 4.49 times higher for nurses in England. It was determined that the rate of depression in ORNs working in Türkiye was 5.97 times higher. It was found that the rate of depression is 1.59 times higher in ORNs living away from the family after care of COVID-19 patient. CONCLUSION: Despite some differences between countries in terms of health system, patient potential, economic and the opportunities offered, generally high levels of anxiety and/or depression indicate that all ORNs need urgent support. Identifying risk factors will help recognize anxiety and depression in ORNs and take measures to protect their mental health during the pandemic.