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Stress is thought to exert both positive and negative effects on cognition, but the precise cognitive effects of social stress and individuals' response to stress remain unclear. We aimed to investigate the association between different measures of social stress and cognitive function in a middle- to older-aged population using data from the European Prospective Investigation into Cancer (EPIC)-Norfolk study.Participants completed a comprehensive assessment of lifetime social adversity between 1993 and 1997 and the short form of the Mini Mental State Examination (SF-MMSE), an assessment of global cognitive function, during the third health check between 2004 and 2011 (a median of 10.5 years later). A low MMSE score was defined as a score in the bottom quartile (20–26).Completed MMSE scores and stress measures were available for 5129 participants aged 48–90 years. Participants who reported that their lives had been more stressful over the previous 10 years were significantly more likely to have low MMSE scores [odds ratio (OR) 1.14, 95% confidence interval (CI) 1.04–1.24 per unit increase in perceived stress], independently of sociodemographic factors, physical and emotional health. The effects were restricted to the highest level of stress and the association was stronger among participants with a lower educational level. Adaptation following life event experiences also seemed to be associated with MMSE scores after adjusting for sociodemographic factors, but the association was attenuated with further adjustment.In this generally high-functioning population, individuals' interpretations and responses to stressful events, rather than the events themselves, were associated with cognitive function.