INTRODUCTION: Preparation for a future pandemic or serious epidemic caused by a known or yet unknown pathogen (Disease X) is a global health priority. Controlled human infection studies (CHIS) are recognised as a valuable tool to accelerate development of vaccines and immunotherapeutics against pathogens with pandemic potential and may play a role in future pandemic settings. The acceptability of CHIS to potential participants in a pandemic setting has not been explored. METHODS: A mixed-methods study of adults screened to participate in a first-in-human SARS-CoV-2 vaccine trial, using online survey and interviews, was undertaken between September and October 2020 in Oxford, UK. This work assessed individuals' views, motivations and experiences of participating in a trial during a pandemic setting, including attitudes towards a hypothetical SARS-CoV-2 CHIS. RESULTS: 349 of 770 (45%) invited individuals completed the survey, and 102 survey respondents (29%) participated in a structured interview. Participants were highly educated, research informed and predominantly of white ethnicity. Approximately a third of survey respondents agreed they would be willing to participate in a hypothetical SARS-CoV-2 CHIS. Individuals aged <35 years old, those without children and those who were single were more likely to agree to participate in a hypothetical SARS-CoV-2 CHIS. This decision was dependent on short-term and long-term complications of infection, availability of rescue therapy, likelihood of CHIS to accelerate vaccine development and urgency of the public health need. Motivations to participate in a SARS-CoV-2 CHIS included altruism and a preference to acquire infection of a circulating pandemic pathogen in a controlled setting. The views of family and friends were important in individuals' decision-making. CONCLUSIONS: Vaccine trial participants are an informed and motivated public group who can provide situated public expertise for CHIS pandemic preparedness. Recruitment to CHIS in a pandemic may be more efficient if targeted to younger, single individuals without children. Media engagement and information specifically for potential CHIS participants' families is important to facilitate informed discussion.