Background: Nurses who work in special care units are at great risk of developing mental health problems. The present study was performed to examine the correlation of religious orientation with depression among critical care and emergency room nurses. Methods: This descriptive, analytical study was performed in 2015 on 109 nurses working in critical care units and emergency rooms of Valiasr and Imam Reza hospitals, Birjand, Iran. The nurses were recruited through census sampling. Data were collected using Beck Depression Inventory and Allport's Religious Orientation Scale. For statistical analysis, independent sample t test, one-way analysis of variance, Tukey's post hoc test, and Pearson's correlation coefficient test were performed, using SPSS v. 16 at a significance level of less than 0.05.