Pandemics such as Covid-19 pose tremendous public health communication challenges in promoting protective behaviours, vaccination, and educating the public about risks. Segmenting audiences based on attitudes and behaviours is a means to increase the precision and potential effectiveness of such communication. The present study reports on such an audience segmentation effort for the population of England, sponsored by the United Kingdom Health Security Agency (UKHSA) and involving a collaboration of market research and academic experts. A cross-sectional online survey was conducted between 4 and 24 January 2022 with 5525 respondents (5178 used in our analyses) in England using market research opt-in panel. An additional 105 telephone interviews were conducted to sample persons without online or smartphone access. Respondents were quota sampled to be demographically representative. The primary analytic technique was k means cluster analysis, supplemented with other techniques including multi-dimensional scaling and use of respondent ‐ as well as sample-standardized data when necessary to address differences in response set for some groups of respondents. Identified segments were profiled against demographic, behavioural self-report, attitudinal, and communication channel variables, with differences by segment tested for statistical significance. Seven segments were identified, including distinctly different groups of persons who tended toward a high level of compliance and several that were relatively low in compliance. The segments were characterized by distinctive patterns of demographics, attitudes, behaviours, trust in information sources, and communication channels preferred. Segments were further validated by comparing the segmentation variable versus a set of demographic variables as predictors of reported protective behaviours in the past two weeks and of vaccine refusal; the demographics together had about one-quarter the effect size of the single seven-level segment variable. With respect to managerial implications, different communication strategies for each segment are suggested for each segment, illustrating advantages of rich segmentation descriptions for understanding public health communication audiences. Strengths and weaknesses of the methods used are discussed, to help guide future efforts.