Abstract Perceived stress impairs cognitive function across the adult lifespan, but the extent to which cognition decline is variable across individuals. Individual differences in the stress response are described as personality traits. Substantial individual differences in the magnitude of cognitive impairment that is induced by short-term perceived stress are poorly understood. The present study tested the hypothesis that the relationship between short-term perceived stress and different aspects of cognition is mediated by personality traits. The study included 1066 participants with behavior and neuroimaging data from the Human Connectome Project after excluding individuals with missing variables. In the result, the parallel multiple mediation model demonstrated that the influence of perceived stress on the total and crystalized cognition is mainly mediated by neuroticism (indirect effect = −0.04, p