Background UK prisons were profoundly affected by the COVID-19 pandemic. Despite this, uptake of the COVID-19 vaccination remained low in these settings. Social roles, relationships, and freedoms influence vaccine uptake. Prisons are isolated by design and may foster mistrust that negatively influences vaccine uptake. Prisons are also unique communities with their own social networks and relationships. Methods We undertook a questionnaire survey across all six prisons in Wales, UK, to gather data on vaccine behaviour, attitudes, and other influencing factors. We fitted binomial generalised linear mixed effects models to identify predictors of vaccination. Results Surveys were completed by 727 prison residents. We found low vaccination uptake in younger cohorts, those serving short sentences, and those who perceived themselves to be in poorer health. Those reporting low levels of trust towards others and those reporting fewer sources of social support in prison were less likely to be vaccinated. Conclusion Our findings suggest that building a prosocial atmosphere in prison and strengthening relationships and trust between prison staff and residents would positively influence vaccine uptake. Specific message framing should be considered to address the beliefs and motivations most prevalent in this population group, rather than focussing simply on enhancing the opportunity for vaccination.