What are the factors that worsen (vs. protect) emotional well-being during a pandemic outbreak such as COVID-19? Through two large-scale nationwide surveys (N1 = 11,131; N2 = 3,000) conducted in China immediately before versus during the coronavirus outbreak, we found that the onset of the coronavirus epidemic led to a 74% drop in overall emotional well-being. Factors associated with the likelihood of contracting the disease (e.g., residing near the epicenter), extent of potential harm (e.g., being an elderly), and relational issues (e.g., those within a marriage) exacerbated the detrimental effect of the outbreak on emotional well-being. Further, individuals’ perception of their knowledge about coronavirus infection was another factor. Regardless of the actual amount of knowledge they possessed, those perceiving themselves as more knowledgeable, were able to experience more happiness during the outbreak. Higher perceived knowledge was associated with a stronger sense of control, which mediated the differences in emotional well-being. These patterns persisted even after controlling for a host of demographic and economic variables. In conclusion, public policies and mental health interventions aimed at boosting/protecting psychological well-being during epidemics should take account of these factors.