Introduction Familial hypercholesterolaemia (FH) is a frequent (1:300) autosomal dominantly inherited condition which causes premature (women <60 years, men <55 years) cardio–cerebrovascular disease (CVD). Early detection and initiation of treatment can prevent the development of CVD and premature death. Our pilot study aims to investigate the prevalence of FH, the feasibility and efficacy of a screening based on a capillary blood test performed during a school medicine visit in primary school children. Methods and analysis In this cross-sectional study, all children (n=3200) between 7 and 12 years, attending primary school in the city of Luxembourg and invited for their mandatory medical school examinations between 2021 and 2023 are invited to participate. A study nurse performs a capillary blood test to analyse the lipid profile. Families receive the result including an interpretation and invitation to seek medical advice if indicated. If FH is confirmed, a reverse cascade screening in that family will be proposed. The child will receive standard care. Primary outcome is the occurrence of confirmed FH in the study population. Secondary outcomes include the percentage of children screened, percentage of children with abnormal lipid values, percentage of families screened and percentage of families with additionally identified members suffering from hypercholesterolaemia. A health economic analysis will be performed. Ethics and dissemination Ethics approval (reference number 202108/01) has been obtained from the National Research Ethics Committee (CNER (Luxembourg)) and was authorised by the ministry of health in Luxembourg. Families receive written information with an informed consent form. Participation requires an informed consent form signed by the parents. The results will be disseminated in peer-reviewed publications, conference presentations and by public media to the general public. Trial registration number NCT05271305 .