PURPOSE: This study aims to assess the content validity, face validity and comprehensiveness of the: (a) EQ-5D-5L, EQ-HWB, and ASCOT SCT4, for adults with rare genetic conditions; (b) the EQ-5D-5L, EQ-HWB, and ASCOT-carer for carers of adults or children with rare genetic conditions; and (c) the EQ-5D-Y-5L carer proxy-complete for children with rare genetic conditions. METHODS: In total, 60 qualitative think-aloud interviews were conducted in Australia and England to understand individuals' thought process during the completion of the QoL measures. Participants were subsequently led through a semi-structured discussion. Transcripts were analysed for whether participants demonstrated understanding of the measures and thematic analysis was conducted on responses to the semi-structured discussion. RESULTS: The majority of participants showed good understanding and supported the validity of the measures for people experiencing rare conditions. For carers, however, a broader evaluative space than health-related QoL was preferred. Several non-health domains were identified as important to both patients and carers, including treatment availability, impact on employment and finance, information and uncertainty, medication and carer burden, impact of passing on a condition, relationships and social connection, and experience with the healthcare system. CONCLUSION: This study provides some support for the face validity and comprehensiveness of the measures for people experiencing rare conditions. However, several participants felt that the narrow health domains were inadequate to capture the breadth of their lived experience. Future research should explore the extent to which the measures capture differences and changes in the QoL domains identified as important to patients and carers.