People from Black and Asian backgrounds are more likely to die from COVID-19 but less likely to be vaccinated, threatening to exacerbate health inequalities already experienced by ethnic minority groups. The literature suggests that mistrust rooted in structural inequality (including socioeconomic position and experience of racism) may be a key barrier to COVID-19 vaccine uptake. Understanding and addressing structural inequality is likely to lead to longer-term impacts than information alone. The aim of this study is to draw on health and sociological theories of structure and agency to inform our understanding of how structural factors influence vaccine confidence. We conducted qualitative interviews and focus groups with 22 people from London and the surrounding areas from December 2021 to March 2022. Fourteen participants were members of the public from ethnic minority backgrounds, and seven were professionals working with the public to address concerns and encourage vaccine uptake. Our findings suggest that people from ethnic minority backgrounds make decisions regarding COVID-19 vaccination based on a combination of how they experience external social structures (including lack of credibility and clarity from political authority, neglect by health services, and structural racism) and internal processes (weighing up COVID-19 vaccine harms and benefits and concerns about vaccine development and deployment). We may be able to support knowledge accumulation through the provision of reliable and accessible information, particularly through primary and community care, but we recommend a number of changes to research, policy and practice that address structural inequalities. These include working with communities to improve ethnicity data collection, increasing funding allocation to health conditions where ethnic minority communities experience poorer outcomes, greater transparency and public engagement in the vaccine development process, and culturally adapted research recruitment processes.