Objective To explore the effectiveness of in situ simulation training on enhancing anesthesia nurses′ emergency response ability to manage respiratory depression during the recovery period after anesthesia. Methods Twenty-one trainees on a nurse anesthesia training program in Hubei Province received in situ simulation that aims to cultivate emergency response ability to manage post-anesthetic respiratory depression. The start-up time of taking measures to manage respiratory depression and time to onset of action, nurses′ technical and non-technical performance scores, as well as their evaluation with the in situ simulation were compared before and after the training. Results The start-up time and time to onset of action were significantly shortened, and the technical and non-technical performance scores as well as the total score were significantly enhanced after the training (P<0.05, P<0.01). Trainees showed high levels of acceptance and satisfaction with the training (greater than 90.0% for all). Conclusion The implementation of in situ simulation improves anesthesia nurses′ technical and non-technical abilities of management of post-anesthetic respiratory depression during the recovery period, which achieves the teaching objective.