AbstractThe COVID-19 pandemic is increasing negative consequences on mental health around the globe. To date, research on what psychological factors could influence individuals’ distress is still scarce. The current study aims to test a multiple mediation model to examine the role of Intolerance of Uncertainty (IU) and emotional regulation (i.e., expressive suppression and cognitive reappraisal) as joint factors, which can increase understanding of psychological distress due to the COVID-19 outbreak. An online survey measuring fear of COVID-19, IU, emotional regulation, and psychological distress was administered to 3863 Italian adults (females 73.3%; M_age = 36.44; SD = 14.74) during lockdown. Results showed that IU partially mediated the effect of fear of COVID-19 on depression, anxiety and stress. Moreover, individuals with difficulties in managing the uncertainties due to their fear of COVID-19 may be at risk for heightened use of expressive suppression and depression. However, individuals with both higher IU and expressive suppression showed lower level of stress. High cognitive reappraisal has a mediational effect on the relationship between fear of COVID-19, IU, and lower psychological distress. Findings suggest that IU and emotional regulation should be targeted for informing the development of tailored treatments to reduce the negative consequences of the outbreak.