Cystic Fibrosis Transmembrane Related Metabolic Syndrome/Cystic Fibrosis Screen Positive, Inconclusive Diagnosis describes children with a positive newborn screen for whom follow-up tests do not confirm CF. Many are healthy carriers, but some will convert to a CF diagnosis; the natural history is not yet well understood. In children with chronic illnesses, unpredictable disease process and limited knowledge of long-term consequences present significant challenges to parental mental health. We wanted to understand the emotional wellbeing of parents with children with CRMS/CFSPID to guide the mental health support offered within the service. Parents were invited to complete validated depression and anxiety screening questionnaires and a short interview. Interview responses were transcribed and analysed using thematic analysis. Thirteen parents from 10 families completed questionnaires and/or the interview. Two of the parents had raised scores on the questionnaires. Our interviews revealed five themes explored here: difficulty adjusting to the label; concern about the future and its uncertainty; fluctuating states of anxiety (subthemes linked to respiratory tract infections and to medical appointments); difficulty explaining the label (subthemes to healthcare professionals and non-healthcare professionals); and satisfaction with the CRMS/CFSPID service. Our data reveal relatively benign scores using objective screening tools, but the qualitative data paints a picture of significant impact on wellbeing. We recommend screening parents from the time their child receives the label, and later the children themselves, for depression and anxiety and signposting to existing resources. Ultimately, a better understanding of the CRMS/CFSPID trajectory may enable us to give families the answers they need.