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This study explored the potential of educational escape rooms (EERs) to replace or supplement clinical simulations in nursing education. Ten baccalaureate nursing students participated in a pilot EER designed around sepsis hypovolemiam care. Pre- and post-tests showed moderate-to-large knowledge improvements (Hedges’ g = 0.69), comparable to gains reported for high-fidelity simulations. Students reported that EERs enhanced teamwork, communication, and application of knowledge but lacked the patient interaction of traditional simulations to some extent. While EERs were seen as engaging and effective instructional strategies, students did not view them as full replacements for clinical simulations. These preliminary findings suggest that well-designed EERs can supplement, but not yet replace, clinical simulations. Future studies with larger samples are recommended to confirm these results.