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Background: Cognitive dysfunction is a well-established manifestation of the post-COVID syndrome. Psychological vulnerability to stressors can modify disease trajectories, causing long-term risk for negative outcomes. Nonetheless, how premorbid risk factors and response to stressor affect neuropsychological changes is still incompletely understood. In this study, we explored the impact of psychosocial variables on cognitive functioning in a post-COVID sample., Methods: All subjects were submitted to a comprehensive neuropsychological battery and an assessment of perceived loneliness, post-traumatic stress, and changes in anxiety and depression levels. A social vulnerability index was also calculated. The set of psycho-social variables was reduced to two Principal Component Analysis (PCA) components: distress and isolation., Results: Forty-five percent of individuals showed cognitive impairments, with predominant memory and executive deficits. Post-traumatic stress disorder was clinically relevant in 44% of the sample. Social vulnerability scores of the sample were comparable to those of general population. The individual performance in learning and response initiation/suppression was directly related to distress component, encasing anxiety, stress, and depression measures., Conclusion: These findings suggest that psychosocial assessment of post-COVID patients can detect fragile individuals at risk of cognitive impairments. Dedicated psychological support services may play a useful role in the prevention of post-COVID cognitive dysfunction., (© 2023. Fondazione Società Italiana di Neurologia.)