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Mechanical circulatory and respiratory support (MCRS) systems provide short- to long-term life support for patients with severe cardiac or respiratory failure. Whereas the challenges of patients with these lifesaving systems are well understood, the challenges faced by nurses of patients receiving MCRS remain relatively unidentified.In this study, we investigated the challenges and experiences of MCRS nurses, with the aim of informing the design of future interventions.A qualitative approach was taken to develop an in-depth understanding of the emotional issues nurses experience in their daily interactions with patients.Nine MCRS nurses ranging in clinical experience were recruited from Australian hospitals.Participants were divided into 3 focus groups, with design prompts being used in the focus groups to facilitate discussion. Data from these focus groups were analyzed through a thematic analysis protocol.The nurses’ accounts were clustered around 2 themes, including (1) patient connection and (2) compassion vitality and fatigue. Each theme elicits a conflicting compromise that MCRS nurses face daily.The challenges of nurses who support patients with MCRS are complex, multifaceted, emotionally stimulating, and exhausting. We therefore contributes a set of design criteria to support such nurses, setting a direction for future research.