INTRODUCTION: The exceptional production of research evidence during the COVID-19 pandemic required deployment of scientists to act in advisory roles to aid policy-makers in making evidence-informed decisions. The unprecedented breadth, scale and duration of the pandemic provides an opportunity to understand how science advisors experience and mitigate challenges associated with insufficient, evolving and/or conflicting evidence to inform public health decision-making. OBJECTIVES: To explore critically the challenges for advising evidence-informed decision-making (EIDM) in pandemic contexts, particularly around non-pharmaceutical control measures, from the perspective of experts advising policy-makers during COVID-19 globally. METHODS: We conducted in-depth qualitative interviews with 27 scientific experts and advisors who are/were engaged in COVID-19 EIDM representing four WHO regions and 11 countries (Australia, Canada, Colombia, Denmark, Ghana, Hong Kong, Nigeria, Sweden, Uganda, UK, USA) from December 2020 to May 2021. Participants informed decision-making at various and multiple levels of governance, including local/city (n=3), state/provincial (n=8), federal or national (n=20), regional or international (n=3) and university-level advising (n=3). Following each interview, we conducted member checks with participants and thematically analysed interview data using NVivo for Mac software. RESULTS: Findings from this study indicate multiple overarching challenges to pandemic EIDM specific to interpretation and translation of evidence, including the speed and influx of new, evolving, and conflicting evidence; concerns about scientific integrity and misinterpretation of evidence; the limited capacity to assess and produce evidence, and adapting evidence from other contexts; multiple forms of evidence and perspectives needed for EIDM; the need to make decisions quickly and under conditions of uncertainty; and a lack of transparency in how decisions are made and applied. CONCLUSIONS: Findings suggest the urgent need for global EIDM guidance that countries can adapt for in-country decisions as well as coordinated global response to future pandemics.