A descriptive survey-based study was undertaken to test the validity and reliability of three scales that are used to assess sedation during opioid administration for pain management: the Inova Health System Sedation Scale (ISS), the Richmond Agitation and Sedation Scale (RASS), and the Pasero Opioid-Induced Sedation Scale (POSS). The study was conducted in a large (830 beds) suburban level I trauma hospital with a random convenience sample of 96 medical-surgical nurses. The study reports: measures of reliability and validity of each scale and significant findings related to correct nursing score and selected actions; nurses' ratings of each scale in terms of combined ease of use; information provided by the scale to inform clinical decisions; and nursing confidence measures. Both the RASS and the POSS demonstrated adequate measures of reliability and validity for measurement of sedation during opioid administration for pain management. However, the POSS scored higher in combined measures of ease of use, nursing confidence, and usefulness of information provided to make clinical decisions. The POSS also yielded the highest percentage agreement with the correct score and correct nursing actions chosen by the nurse among the three scales tested. Study results have clinical significance for accuracy of clinical assessments and subsequent actions on behalf of patients experiencing advancing sedation during opioid analgesia. The POSS can be recommended as a superior sedation scale for the measurement of sedation during opioid administration for pain management.