An “online respiratory infectious disease nursing simulation course” was developed to strengthen the nursing competency in respiratory infectious disease. Methods: In this methodological study, an “online respiratory infectious disease nursing simulation course” was developed using the ADDIE (Analysis, Design, Development, Implementation, and Evaluation) model and evaluated using a one-group pre-post quasi-experimental design to ascertain the respiratory infectious disease knowledge, performance confidence, and clinical performance of 37 nursing students. Results: The online course comprised 17 sessions categorized as follows: seven theory, five at-home laboratory training, two case study, and three simulation sessions. All the nursing students engaged in the course successfully fulfilled its requirements by attending all 17 sessions and passing the clinical performance examination. The knowledge, confidence, and clinical performance (t=-6.60, -10.62, and –6.36, respectively; p<.001 for all) pertaining to respiratory infectious disease significantly increased among participants after the concluding simulation session, compared with their pre-scores obtained prior to the course participation. Conclusion: The “online respiratory infectious disease nursing simulation course” significantly improved the nursing knowledge, performance confidence, and clinical performance ability of nursing students in managing respiratory infectious diseases.