Abstract Background Although telemedical applications are increasingly used in the area of both mental and physical illness, there is no quality of life (QoL) instrument that takes into account the specific context of the healthcare setting. Therefore, the aim of this study was to determine a concept of quality of life in telemedical care to inform the development of a setting-sensitive patient-reported outcome measure. Methods Overall, 63 semi-structured single interviews and 15 focus groups with 68 participants have been conducted to determine the impact of telemedical care on QoL. Participants were patients with chronic physical or mental illnesses, with or without telemedicine supported healthcare as well as telemedical professionals. Mayring's content analysis approach was used to encode the qualitative data using MAXQDA software. Results The majority of aspects that influence the QoL of patients dealing with chronic conditions or mental illnesses could be assigned to an established working model of QoL. However, some aspects that were considered important (e. g. perceived safety) were not covered by the pre-existing domains. For that reason, we re-conceptualized the working model of QoL and added a sixth domain, referred to as healthcare-related domain. Conclusion Interviewing patients and healthcare professionals brought forth specific aspects of QoL evolving in telemedical contexts. These results reinforce the assumption that existing QoL measurements lack sensitivity to assess the intended outcomes of telemedical applications. We will address this deficiency by a telemedicine-related re-conceptualization of the assessment of QoL and the development of a suitable add-on instrument based on the resulting category system of this study.