BackgroundVaccine hesitancy is a concerning public health issue, further amplified during the COVID-19 pandemic. Social media is an important player in this context, promoting the dissemination of both information and misinformation. Qualitative studies analyzing the meaning of social media contents in correlation with epidemiological data are scarce, and could aid our understanding of social media's impact on vaccine hesitancy. MethodsIn this study, we identified open-ended responses on reasons to refuse the COVID-19 vaccine collected in an epidemiologic study, and analyzed meaning relations with Twitter posts according to theme categories using a qualitative approach. ResultsAmong responses to open-ended questions on motivations for refusing the COVID-19 vaccine, we identified and analyzed five theme categories: 1. individuality; 2. fear of adverse events/distrust in vaccine safety; 3. political ideologies/aversion to recommendations issued by the State; 4. skepticism about vaccine efficacy; and 5. refusal of non-natural products or interventions. We observed a close correspondence between open-ended responses in the epidemiological study and Twitter posts in all 5 theme categories. The highest outreach of Twitter posts was observed for those in the “individuality” and “fear of adverse the events/distrust in vaccine safety” theme categories. ConclusionsOur study suggests that social media interactions can perpetuate misinformation and hesitant attitudes about vaccines. Social media algorithms can intensify ideologic isolation, and strategies to promote the dissemination of tailored health information among social media users should be implemented to promote an overall understanding of health, particularly those concerning the collective wellbeing.