Background Hong Kong's 3-year dynamic zero-COVID policy has caused prolonged exposure to stringent, pervasive anti-epidemic measures, which poses additional stressors on emotional well-being through pandemic fatigue, beyond the incumbent fear of the pandemic.Aims To investigate how major policy shifts in the zero-COVID strategy have corresponded with changing relationships between emotional well-being, pandemic fatigue from policy adherence, and pandemic fear, following the pandemic peak to a living-with-COVID policy.Method A three-wave repeated cross-sectional study (N = 2266) was conducted on the Chinese working-age population (18-64 years) during the peak outbreak (Wave 1), and subsequent policy shifts towards a living-with-COVID policy during the initial relaxation (Wave 2) and full relaxation (Wave 3) of anti-epidemic measures from March 2022 to March 2023. Non-parametric tests, consisting of robust analysis of covariance tests and quantile regression analysis, were performed.Results The severity of all measures was lowered after Wave 1; however, extreme pandemic fears reported in Wave 2 (n = 38, 7.7%) were associated with worse emotional well-being than the pandemic peak (Wave 1), which then subsided in Wave 3. Pandemic fatigue posed greater negative emotional well-being in Wave 1, whereas pandemic fear was the dominant predictor in Waves 2 and 3.Conclusions Pandemic fatigue and pandemic fear together robustly highlight the psychological cost of prolonged pandemic responses, expanding on a framework for monitoring and minimising the unintended mental health ramifications of anti-epidemic policies.