•Source isolation and quarantine for infectious diseases is associated with a range of intended and unintended consequences.•Patients in isolation quarantine with SARS-CoV-2 and COVID-19 report a range of positive and negative intended and unintended consequences.•Personal planning, access to information, social and family resources, communication and the physical environment are significant mediators of the patient experience of isolation and quarantine. Isolation and quarantine are key measures in outbreak management and disease control. They are, however, associated with negative patient experiences and outcomes, including an adverse impact on mental health and lower quality of care due to limited interaction with healthcare workers. In this study, we explore the lived experience and perceptions of patients in isolation with COVID-19 in an Australian healthcare setting. Using a phenomenological approach from a Heideggerian hermeneutical perspective, we conducted individual semistructured interviews with the first 11 COVID-19 patients admitted to a designated COVID-19 facility in Australia. Interviews were audiorecorded, transcribed verbatim, and imported into NVivo 12 for coding and analysis. Participants’ lived experience and perceptions of COVID-19 were represented by 5 themes: “Knowing about COVID-19,” “Planning for, and responding to, COVID-19,” “Being infected,” “Life in isolation and the room,” and “Post-discharge life.” Within these, participants conveyed both positive and negative lived experiences of infection, isolation, and illness. The contextual aspects of their social and physical environment together with their individual resources contributed to the framing of their planning for, and response to, the outbreak, and were important mediators in their experience. Findings from this study provide a valuable insight into the lived experiences of patients with COVID-19, which reflect those of patients with other infectious diseases who require isolation.