question: Improving nursing students' understanding of the novel COVID-19 is an essential component of their education. We designed and developed a serious game-based computer learning application that requires nursing students to solve problems through simulated cases. This study aimed to compare knowledge mastery among nursing students who used this teaching method versus those who received online lectures. A retrospective observational study was conducted using preclass, postclass, and final test scores of 130 students retrieved from the university's database of test scores. Both teaching methods produced significant increases in short-term knowledge of COVID-19. There was no statistical difference between the two methods in pre- and postclass scores; however, the serious game group scored higher than the online lecture group in knowledge retention. In summary, the serious game application is a potentially effective method for COVID-19 education among nursing students, particularly in terms of its capacity for improved knowledge retention.