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As the COVID-19 pandemic extends into another year, the causes and consequences of pandemic fatigue and vaccine hesitancy have become prominent concerns. This dataset contains MTurk survey responses from 658 vaccinated USA samples indicating: (a) pandemic fatigue and psychological distress (physical and trauma symptoms); (b) delays in receiving medical care due to COVID-19 restrictions; (c) vaccine-related behavior and beliefs (type of vaccine and vaccine hesitancy), and (d) COVID-19 preventive health behaviors. Several predictor variables were also collected including: (a) demographic variables; (b) COVID-19 health risk factors; (c) perceived susceptibility to disease and intolerance of uncertainty; (d) attitudes, subjective norms and perceived behavioral control about COVID-19 vaccine from the theory of planned behavior; (e) compassion for self and others; (f) psychological flexibility and inflexibility; (g) Buddhist mindfulness insight (impermanence, acceptance of suffering, nonself attachment, mindfulness); and (h) cultural orientation and authoritarianism. The data were collected between August 28th and October 18th of 2021. Out of the 746 MTurk workers who responded to the survey, 88 were removed from the dataset due to failing attention checks and problems with quality data. The responses from the remaining 658 allow an examination of the associations between fatigue and distress from COVID-19; COVID-19 vaccine related behaviors and beliefs; preventive health behaviors for COVID-19; COVID-19 susceptibility; intolerance of uncertainty; together with compassion, psychological flexibility, mindfulness, cultural orientation, as well as authoritarianism as possible moderators of COVID-19 fatigue, distress, and vaccine beliefs., Competing Interests: All authors declare that they have no known competing financial interests or personal relationships which have, or could be perceived to have, influenced the work reported in this article., (© 2022 The Authors.)