Host specificity of fleas affects their biodiversity that plays a major role in determining the potential transmission routes by pathogens through vertebrate hosts, including humans. In the Biogeographic Andean region, numerous systematic and ecological studies have been conducted, revealing a high diversity of flea taxa of mammals and the presence of pathogenic organisms transmitted by fleas; however, the degree of preference with which each flea species associates with a mammal host remains poorly understood in this region. Herein, host specificity in mammal fleas from the Andean region was analysed. We employed the number of host species for each flea species and the index of host specificity STD *. Following the literature, 144 species and 13 subspecies of fleas (31 genera and 10 families) have been described in the Andean biogeographic region; 76 taxa are endemic to this region. To carry out the analyses of host specificity, we considered 1759 records of fleas collected from 124 species and 59 genera of wild and domestic mammals, mostly rodent species (85.9%). Our results indicate that typical Andean fleas are genus or family host specific (mostly STD * less than 3.0). More diverse mammal hosts are parasitized by more diverse flea genera and families and these hosts are phylogenetically related. Otherwise, these hosts are associated with different flea lineages, suggesting the interaction of ecological and evolutionary mechanisms (host-switching, ecological adaptations and co-evolutionary alternation). The fields of disease ecology and One Health are considering the host specificity of arthropod vectors as an important point to understand the mechanisms of emergence and re-emergence of diseases. Our results allow us to estimate the risk of diseases involving fleas in the Andean region.