Unparalleled levels of misinformation have contributed to widespread misunderstandings about the nature of the coronavirus, its cure and preventative measures. Misinformation crosses borders rapidly with the help of social media, and this phenomenon is constantly increasing. Thus, the current study proposes a research framework to explore how citizens’ trust in government and social media influences their readiness to follow COVID-19 preventive measures. Additionally, the role of a health infodemic was explored in perceptions and relationships among factors influencing an individual’s readiness to follow COVID-19 preventive measures with data collected from 396 participants in Taiwan. The findings indicate citizens’ trust in social media (TRSM), attitude (ATT), perceived benefit (PBT), personal innovativeness, and how peer referents positively influence their readiness. However, the relationship between citizens’ trust in the government (TRGT) and their readiness to follow COVID-19 preventive measures (INT) is not statistically significant. The current study also explores the negative moderating effect of health infodemics on the relationship between TRSM and INT, TRGT and INT, ATT and INT, PBT and INT. Thus, the Taiwanese government must consider the current study’s findings to develop attractively, informed, and evidence-based content, which helps its citizens improve their health literacy and counter the spread of misinformation.