BackgroundVaccine hesitancy has gained heightened relevance amid the COVID-19 pandemic, underscoring the urgency of understanding its determinants. This study explores the association between Covid-19 vaccine hesitancy, mental health variables and inflexible thinking. MethodsA convenience sample of 252 UK adults was assessed online between June 2021–July 2022 (when Covid-19 lockdown restrictions had finally eased). We assessed participants using the Oxford Covid Vaccine Hesitancy Scale (OCVHS), various aspects of mental health, using: the Obsessive-Compulsive Inventory-Revised (OCI-R), Compulsive Personality Assessment Scale (CPAS), Depression, Anxiety, and Stress scale (DASS-21), and finally, performance on a computerized version of the Wisconsin Card Sort Task (WCST). This study was preregistered at the Open Science Framework (https://osf.io/xd5wz). ResultsMultiple regression analyses showed that only cognitive inflexibility, and specifically the WCST item of perseverative errors, significantly predicted vaccine hesitancy. ConclusionOur exploratory analysis provides the first evidence that cognitive inflexibility, measured using an objective task, is an independent risk-factor for vaccine hesitancy. Public health strategies should consider the impact of an inflexible thinking style on the decision-making of those most at risk of vaccine hesitancy and adapt interventions accordingly.