The new Coronavirus has been declared a global pandemic by the World Health Organization. The sudden outbreak of this new virus and the measure of lockdown adopted to contain the epidemic have profoundly changed the lifestyles of the Italian population, with an impact on people’s quality of life and on their social relationships. In particular, due to forced and prolonged cohabitation, couples may be subject to specific stressors during the epidemic. In addition, living with a chronic health condition may add (...) specific challenges to the ones posed by the epidemic itself. The present cross-sectional study aimed to provide a picture of the challenges as well as the resources for both individual and relational well-being of Italian individuals in a couple relationship, with a specific attention to the comparison between individuals living with and without a chronic disease. Results showed that people with a chronic disease had lower psychological well-being and more fears and worries about the COVID-19. People with a chronic disease perceived fewer resources than healthy people. Moreover, the challenges are shown to be associated with less psychological well-being and high pessimism about the future. Instead individual, relational, and social resources play a protective role during the pandemic for both healthy and chronically ill people. (shrink)