An altered stress response can contribute to the transition from preclinical psychotic symptoms to the clinical manifestation of schizophrenia and other psychotic disorders. The present study was aimed at testing the hypotheses that (i) the autonomic and neuroendocrine responses under psychosocial stress are dysregulated in individuals with high psychosis proneness (schizotypy); (ii) the magnitude of post-stress autonomic activation and cortisol release predicts alterations in semantic memory retrieval. The study was performed in 73 healthy individuals of both sexes with either high or low schizotypal traits preselected out of 609 individuals using the Schizotypal Personality Questionnaire. A psychosocial stress procedure based on public speech was used as a stress model. We found that individuals with high schizotypy engaged in less adaptive emotional stress-coping strategies than low schizotypy individuals. Yet, the neuroendocrine, immune, and sympathetic activation in response to the stress test was not different between the groups. Irrespective of the exposure to the stressor, individuals with high schizotypy were less fluent when retrieving associations from semantic memory. In addition, we demonstrated that acute psychosocial stress reduced the flexibility of semantic memory retrieval. The post-stress mental inflexibility was reliably predicted by the concomitant elevation of cortisol concentrations in saliva. The present study thus brings novel evidence indicating that the acute psychosocial challenge impairs retrieval flexibility in the semantic domain, which may be due to neuroendocrine activation.Copyright © 2023 Elsevier Ltd. All rights reserved.