Although widely used, area-based deprivation indices remain sensitive to urban-rural differences as such indices are usually standardised around typical urban values. There is, therefore, a need to determine to what extent available deprivation indices can be used legitimately over both urban and rural areas. This study was carried out in Brittany, France, a relatively affluent region that contains deep rural areas. Among the 1,736 residential census block groups (IRIS) composing the Brittany region, 1,005 (57.9%) are rural. Four deprivation indices were calculated: two scores (Carstairs and Townsend) developed in the UK and two more recent French measures (Havard and Rey). Two standardisation levels were considered: all of the IRIS and only the urban IRIS of the region. Internal validity (Kappa coefficients and entropy values) and external validity (relationship with colorectal cancer screening CCS attendance) were investigated. Regardless of the deprivation measure used, wealthy areas are mostly clustered in the West and at the outskirts of major towns. Carstairs and Rey scores stand out by all evaluation criteria, capturing both urban and rural deprivation. High levels of agreements were found across standardisation levels (κ = 0.96). The distributions of deprivation scores were balanced across urban and rural areas, and high Shannon entropy values were observed in the capital city (≥0.93). Similar and significant negative trends were observed between CCS attendance and both deprivation indices, independent of the degree of urbanisation. These results provide support, despite potential sociological objections, for the use of a compromise index that would facilitate comparisons and interpretations across urban and rural locations in public health research.