Entrepreneurial Ecosystem (EE) is a novel perspective to analyze the interplay between support systems and businesses in regions. Simultaneously, universities have been playing increasingly important roles in entrepreneurship, fostering economic growth both through the wider regional economy (RE) and their own University EEs (UEEs). Entrepreneurs in Residence (EiRs), chosen by universities as exemplar entrepreneurs, therefore provide potentially important conduits between the regional economy, UEEs and entrepreneurs, leading us to explore how and why do EiRs and universities interact in relation to entrepreneurial ecosystems to enhance regional economy? Our qualitative study of a UK university case, conducted in the context of the Covid-19 pandemic which severely impacted many businesses’ access to resources, gives a particular temporal context to this research. It identifies accessing resources, building legitimacy and undertaking bridging activities as the three highest-level dimensions characterising EiR-University interactions, which have relevance for both the UEE and regional economy more widely, offering a framework for future EiR programmes. This study contributes to the regional entrepreneurship and EE literature, by examining the role of regional universities as anchor tenants and catalysts of entrepreneurial growth and resilience within regions, and calls for further research into the evolution of EiR-university interactions in different institutional contexts.