The world has been fighting with the novel COVID-19 pandemic, which has scientific, societal, and ethical components, and thus it can be classified as one of the most challenging socio-scientific issues (SSI) of our era. The pandemic required individuals to make decisions on a variety of issues, and these decision-making processes are highly related to informal reasoning and individuals' scientific literacy (SL). Thus, this paper aims to investigate the N = 26 pre-service biology teachers' informal reasoning and decision-making modes within the real-time and dynamic COVID-19 pandemic context. The present study revealed that most of the participants made rationalistic based decisions about COVID-19 and social isolation. Moral-based decision-making, which is second-highest frequency among all decision-making modes, is also specific to COVID-19 and social isolation. Furthermore, the participants utilized different arguments while self-reasoning on the issue and convincing someone of their ideas about social isolation and COVID-19.