Background: The Covid-19 pandemic raises questions about the role that relationships and interactions between humans and animals play in the context of widespread social distancing and isolation measures. We aimed to investigate links between mental health and loneliness, companion animal ownership, the human-animal bond, and human-animal interactions; and to explore animal owners’ perceptions related to the role of their animals during lockdown. Methods: A cross-sectional online survey of UK residents over 18 years of age was conducted between April and June 2020. The questionnaire included validated and bespoke items measuring demographics; exposures and outcomes related to mental health, wellbeing and loneliness; the human-animal bond and human-animal interactions. Results: Of 5,926 participants, 5,323 (89.8%) had at least one companion animal. Most perceived their animals to be a source of considerable support, but concerns were reported related to various practical aspects of providing care during lockdown. Strength of the human-animal bond did not differ significantly between species. Poorer mental health pre-lockdown was associated with a stronger reported human-animal bond (b = -.014, 95% CI [-.023 – -.005], p = .002). Animal ownership compared with non-ownership was associated with smaller decreases in mental health (b = .267, 95% CI [.079 – .455], p = .005) and smaller increases in loneliness (b = -.302, 95% CI [-.461 – -.144], p = .001) since lockdown. Conclusion: The human-animal bond is a construct of potential clinical importance to identify mental health vulnerability in animal owners. Animal ownership appeared to mitigate some of the detrimental psychological effects of lockdown. Further targeted investigation of the role of human-animal relationships and interactions for human health, including testing of the social buffering hypothesis and the development of instruments suited for use across animal species, is required.