Little is known about which communication strategies nurses carried out and whether the nurse–patient relationship has been altered due to the mandated use of personal protective equipment during the COVID-19 pandemic. This study describes how nurse–patient communication and relationships took place from the point of view of nurses engaged in caring for patients with COVID-19. A qualitative descriptive study design following COREQ guidelines was conducted. Semi-structured telephone interviews with nurses working in the COVID ward of an Italian university hospital were performed between September 2020 and June 2021. Ten nurses were recruited using convenience sampling. One overarching theme, three main themes, and nine sub-themes were identified. The overarching theme ‘The in-out relationship: ‘in here and out there’ and ‘inside me and out of me’ included the main themes ‘A closed system different from normal’, ‘Uncovering meaningful human gestures’, and ‘A deep experience to live’’. The relational nature of nursing—where ‘me and you’ and the context are the main elements—leads nurses to find new ways of interacting and communicating with patients, even in a new situation that has never been experienced. Enhancing human gestures, thinking about new contexts of care, and educating new generations to maintain human-to-human interaction, regardless of the context of care, are the directives to be explored for creating the future of nursing care.