Background: In the absence of treatments and vaccines, the mitigation of COVID-19 relies on population engagement in non-pharmaceutical interventions, which is driven by their risk perception, anxiety HP level and knowledge. There may also be regional discrepancies in these drivers due to different historical exposure to disease MESHD outbreaks, government responses and cultures. As such, this study compared psycho-behavioral responses in two regions during the early phase of the pandemic. Methods: Comparable cross-sectional surveys were administered among adults TRANS in Hong Kong (HK) and the United Kingdom (UK) during the early phase of each respective epidemic. Explanatory variables included demographics, risk perception and knowledge of COVID-19, anxiety HP level and preventive behaviors. Responses were weighted according to census data. Logistic regression models, including interaction terms to quantify regional differences, were used to assess the association between explanatory variables and the adoption of social-distancing measures. Results: Data of 3431 complete responses (HK:1663; UK:1768) were analysed. Perceived severity differed by region (HK: 97.5%; UK: 20.7%). A large proportion of respondents were abnormally/borderline anxious (HK:64.8%; UK:45.9%) and regarded direct contact with infected individuals as the transmission TRANS route of COVID-19 (HK:94.0-98.5%; UK:69.2-93.5%), with HK identifying additional routes. HK reported high levels of adoption of social-distancing (HK:32.4-93.7%; UK:17.6-59.0%) and mask-wearing (HK:98.8%; UK:3.1%). The impact of perceived severity and perceived ease of transmission TRANS on the adoption of social-distancing varied by region. In HK, they had no impact, whereas in the UK, those who perceived severity as 'high' were more likely to adopt social-distancing (aOR:1.58-3.01), and those who perceived transmission TRANS as 'easy' were prone to both general social-distancing (aOR:2.00, 95% CI:1.57, 2.55) and contact avoidance (aOR:1.80, 95% CI: 1.41, 2.30). The impact of anxiety HP on adopting social-distancing did not vary by region. Discussion: These results suggest that health officials should ascertain and consider baseline levels of risk perception and knowledge in the populations, as well as prior sensitisation to infectious disease MESHD outbreaks, during the development of mitigation strategies. Risk communication should be done through suitable media channels - and trust should be maintained - while early intervention remains the cornerstone of effective outbreak response.