Scientific evidence plays an important role in the therapeutic decision-making process. What happens when physicians are forced to make therapeutic decisions under uncertainty? The absence of scientific guidelines at the beginning of a pandemic due to an unknown virus, such as COVID-19, could influence the perceived legitimacy of the application of non-evidence-based therapeutic approaches. This paper reports on a test of this hypothesis, in which we administered an ad hoc questionnaire to a sample of 64 Italian physicians during the first wave of the COVID-19 pandemic in Italy (April 2020). The questionnaire statements regarding the legitimacy of off-label or experimental drugs were framed according to three different scenarios (Normality, Emergency and COVID-19). Furthermore, as the perception of internal bodily sensations (i.e., interoception) modulates the decision-making process, we tested participants' interoceptive sensibility using the Multidimensional Assessment of Interoceptive Awareness (MAIA). The results showed that participants were more inclined to legitimate non-evidence-based therapeutic approaches in the COVID-19 and Emergency scenarios than the Normality scenario. We also found that scores on the MAIA Trusting subscale positively predicted this difference. Our findings demonstrate that uncertain medical scenarios, involving a dramatic increase in patient volume and acuity, can increase risk-taking in therapeutic decision-making. Furthermore, individual characteristics of health care providers, such as interoceptive ability, should be taken into account when constructing models to prevent the breakdown of healthcare systems in cases of severe emergency.