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Abstract ObjectivesWe conducted interviews with state epidemiologists involved in the state-level COVID-19 response to understand the challenges and opportunities that state epidemiologists and state health departments faced during COVID-19 and consider the implications for future pandemic responses. MethodsAs part of a broader study on policymaking during COVID-19, we analyzed 12 qualitative interviews with state-epidemiologists from 11 US states regarding the challenges and opportunities they experienced during the COVID-19 response. ResultsInterviewees described the unprecedented demands COVID-19 placed on them, including increased workloads as well as political and public scrutiny. Decades of under-funding and constraints posed particular challenges for meeting these demands and compromised state responses. Emergency funding contributed to ameliorating some challenges. However, state health departments were unable to absorb the funds quickly, which created added pressure for employees. The emergency funding also did not resolve longstanding resource deficits. ConclusionsState health departments were not equipped to meet the demands of a comprehensive COVID-19 response, and increased funding failed to address shortfalls. Effective future pandemic responses will require sustained investment and adequate support to manage on-going and surge capacity needs. Increased public interest and skepticism complicated the COVID-19 response, and additional measures are needed to address these factors.