This study investigated whether life satisfaction and cognitive distortions mediate the relationship between perceived stress and cognitive flexibility in adults, with particular attention to implications for psychological well-being and clinical practice. This research article reports a quantitative empirical study employing a cross-sectional survey design and regression-based bootstrapped parallel mediation analysis. Using a cross-sectional design, data were collected from 330 adults aged 18 to 63 years recruited from community and healthcare settings. Mediation analyses were performed using regression-based bootstrapping procedures. Perceived stress showed a significant and negative association with cognitive flexibility, representing a medium effect size. Higher levels of perceived stress predicted lower life satisfaction and higher levels of cognitive distortions, both of which were in turn linked to reduced cognitive flexibility. The combined indirect effects accounted for approximately forty percent of the overall association between stress and cognitive flexibility, indicating substantial mediating influence. Specifically, mediation through life satisfaction and cognitive distortions demonstrated meaningful contributions to the model. These findings highlight the importance of addressing subjective well-being and maladaptive cognitive patterns in stress-related interventions. Supporting individuals in enhancing cognitive flexibility may serve as a protective mechanism against the adverse psychological and health consequences of stress, and may also contribute to improved treatment adherence and chronic disease management within clinical contexts. By jointly testing a protective mediator (life satisfaction) and a risk mediator (cognitive distortions) within one model, the study extends prior single-mediator approaches and offers an integrated explanation of the perceived stress–cognitive flexibility relationship.

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