<sec> <title>Objectives</title> <p>The Korea Centers for Disease Control and Prevention has published “A Guideline for Unknown Disease Outbreaks (UDO).” The aim of this report was to introduce tabletop exercises (TTX) to prepare for UDO in the future.</p></sec> <sec> <title>Methods</title> <p>The UDO Laboratory Analyses Task Force in Korea Centers for Disease Control and Prevention in April 2018, assigned unknown diseases into 5 syndromes, designed an algorithm for diagnosis, and made a panel list for diagnosis by exclusion. Using the guidelines and laboratory analyses for UDO, TTX were introduced.</p></sec> <sec> <title>Results</title> <p>Since September 9^th, 2018, the UDO Laboratory Analyses Task Force has been preparing TTX based on a scenario of an outbreak caused by a novel coronavirus. In December 2019, through TTX, individual missions, epidemiological investigations, sample treatments, diagnosis by exclusions, and next generation sequencing analysis were discussed, and a novel coronavirus was identified as the causal pathogen.</p></sec> <sec> <title>Conclusion</title> <p>Guideline and laboratory analyses for UDO successfully applied in TTX. Conclusions drawn from TTX could be applied effectively in the analyses for the initial response to COVID-19, an ongoing epidemic of 2019 – 2020. Therefore, TTX should continuously be conducted for the response and preparation against UDO.</p></sec>