Deprivation indices are used to monitor health inequities. However, their theoretical underpinnings have been based on the context of Western industrialized countries, which have distinct social and historical backgrounds compared to Latin America and the Caribbean and countries in the Global South. Following the Latin American Social Determination of Health perspective, particularly the category Modes of Living supported by the construct of precarity, we aimed to develop an index of precarity in the modes of living at the department level in Colombia and assess its geographical distribution and potential value for public health. We conducted an ecological cross-sectional study with national administrative records. We developed a precarity index through Principal Component Analysis and performed spatial autocorrelation analyses and regression models with child mortality indicators. Our final index comprised twenty indicators representing four dimensions of the modes of living and power relations. We found precarity not to distribute randomly in Colombia, with a center-periphery divide and higher precarity observed in the country’s margin. We also found an association of our index with under-five mortality (SMR = 1.19; 95%CI 1.08–1.31) and infant mortality (SMR = 1.13; 95%CI 1.00–1.26). Our index highlights the relevance of considering the modes of living when devising deprivation indices or similar measures from Colombia or Latin America. This approach may provide different perspectives on the health-disease process and potential value for public health planning.