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Background: This study aimed to evaluate the effectiveness of a digital serious game intervention about COVID-19 on pre-registration nursing student knowledge. Method: This study included 282 nursing students from a university in Northern Ireland, with 210 students providing comparable pre-test and post-test results. The ‘serious game’ aimed to debunk common COVID-19 myths and provide accurate information about the virus. Participants completed a 25-item questionnaire before and after engaging with the game, which included true/false items based on the World Health Organisation’s list of top COVID-19 myths. The data were analysed using paired t-tests to assess knowledge changes, and scores were calculated as percentages of correct answers. Results: A statistically significant improvement in COVID-19 knowledge was demonstrated among first-year nursing students who engaged with the serious game. The post-test scores (M = 92.68, SD = 13.59) were notably higher than the pre-test scores (M = 82.64, SD = 13.26), with a p-value less than 0.001. Conclusion: This research suggests that integrating serious games into undergraduate nursing education can effectively enhance COVID-19 knowledge. This approach is aligned with the evolving trend of employing technology and gamification in healthcare education.