Background: Monitoring the presence of commensal and pathogenic microorganisms in the human oral, nasal and hand niches as determinants for respiratory tract infections is of critical global relevance as was evident during the COVID-19 pandemic. However, community-based surveillance is difficult because current sampling methods are not optimal for a wide age range of participants, particularly young children. We designed a platform of minimally invasive self-sampling at home and assessed its use for longitudinal monitoring of the oral, nasal and hand microbiota of adults and children within families. Methods: Healthy families with two adults and up to three children, living in and near Liverpool, United Kingdom, self-collected saliva, nasal lining fluid using synthetic absorptive matrices and hand swabs at home every two weeks for six months. Questionnaires were used to collect demographic and epidemiological data and assess feasibility and acceptability. At the end of the study, participants were invited to take part in an interview. Results: Thirty-three families completed the study. Sample collection using our approach was acceptable to 25/33 (76%) families, as sampling was fast (76%), easy (76%) and painless (60%). Saliva and hand sampling was acceptable to all participants of any age, whereas nasal sampling was accepted mostly by adults and children older than 5 years. Conclusion: Multi-niche self-sampling at home can be used by adults and children for longitudinal microbial surveillance, providing key data for monitoring respiratory infections.