Funding Information: TK, LWH, TN, SD, KPG, AV, TGV, NV, CV, CG and CVR declare receiving a grant by Fonds Wetenschappelijk Onderzoek (FWO-Research Foundation – Flanders), to conduct social listening of vaccine concerns in Belgium. LWH, NV, TGV, KPG, CG, CVR, SD, and TN declare receiving funds by the Vaccine Confidence Fund to conduct a study on healthcare workers vaccine sentiments and to foster vaccine dialogue in Belgium. HJL reports receiving a grant by MacArthur Foundation to address inequalities in Covid-19 recovery, by J&J to listening to public concerns around Covid-19, from Unicef to carry out social media listening of vaccine concerns in Central and Eastern Europe, and by Merck for research on vaccine hesitancy among health care providers in 15 countries. Publisher Copyright: © 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. ; The COVID-19 pandemic has disrupted societies globally. Public health institutions were tasked with responding to the pandemic in a dynamic and uncertain context. This paper sheds light on the experiences of COVID-19 response actors as they navigated multi-dimensional crises associated with the pandemic in general and vaccine hesitancy in particular. This research was conducted during the initial phase of the COVID-19 vaccine rollout in Flanders, Belgium. Participants included informants across all levels of the COVID-19 vaccination strategy including but not limited to those producing scientific knowledge, providing policy input, or implementing public health directives locally. ‘Crisis’ was identified as a recurring theme in interviews with informants. The paper highlights multi-dimensional crises experienced by informants such as the: (i) crisis of prioritization, (ii) crisis of communication, (iii) crisis of the changing image of science, (iv) crisis of epistemic agency and autonomy, and (v) crisis of trust. ; publishersversion ; published