The possibility that a multi-host wildlife reservoir is responsible for maintaining transmission of Leishmania (Viannia) braziliensis causing human cutaneous and mucocutaneous leishmaniasis is tested by comparative analysis of infection progression and infectiousness to sandflies in rodent host species previously shown to have high natural infection prevalences in both sylvatic or/and peridomestic habitats in close proximity to humans in northeast Brazil. The clinical and parasitological outcomes, and infectiousness to sandflies, were observed in 54 colonized animals of three species (18 Necromys lasiurus, 18 Nectomys squamipes and 18 Rattus rattus) experimentally infected with high (5.5×106/ml) or low (2.8×105/ml) dose L. (V.) braziliensis (MBOL/BR/2000/CPqAM95) inoculum. Clinical signs of infection were monitored daily. Whole animal xenodiagnoses were performed 6 months post inoculation using Lutzomyia longipalpis originating from flies caught in Passira, Pernambuco, after this parasite evaluation was performed at necropsy. Heterogeneities in Leishmania parasite loads were measured by quantitative PCR in ear skin, liver and spleen tissues. All three rodent species proved to establish infection characterized by short-term self-resolving skin lesions, located on ears and tail but not on footpads (one site of inoculation), and variable parasite loads detected in all three tissues with maximum burdens of 8.1×103 (skin), 2.8×103 (spleen), and 8.9×102 (liver). All three host species, 18/18 N. lasiurus, 10/18 N. squamipes and 6/18 R. rattus, also proved infectious to sandflies in cross-sectional study. R. rattus supported significantly lower tissue parasite loads compared to those in N. lasiurus and N. squamipes, and N. lasiurus appeared to be more infectious, on average, than either N. squamipes or R. rattus. A multi-host reservoir of cutaneous leishmaniasis is indicated in this region of Brazil, though with apparent differences in the competence between the rodent species. The results provide preliminary insights into links between sylvatic and peri-domestic transmission cycles associated with overlaps in the rodent species’ ecological niches. Across the Americas, Leishmania (V.) braziliensis is the predominant Leishmania species causing cutaneous and mucocutaneous leishmaniasis in humans. Transmitted by Phlebotomine sandflies, questions remain about the epidemiological contributions of the numerous zoonotic and more domestic host species. Domestication of the principal vector and human infection patterns suggest that human infection risk is predominantly peridomestic, whereas control strategies will be more complex if there is a link to a wildlife transmission cycle. Almost no studies have been conducted on the transmission potential of natural hosts of L. (V.) braziliensis. This study evaluates the infectiousness of experimentally infected natural rodent host species, that in different ecological habitats are proposed to act as a single or a multi-host reservoir. Clinical and parasitological development, and the ability to transmit Leishmania to sandflies, was observed under experimental conditions using a single strain of L. (V.) braziliensis isolated from the wild rat, Necromys lasiurus. Xenodiagnoses were performed with laboratory bred sand fly females established from a local population of Lutzomyia longipalpis. All three rodent species developed disseminated subclinical parasitological infections, but clinical signs (lesions) were transient and self-resolving. N. squamipes, N. lasiurus and R. rattus were all infectious when asymptomatic, though their competence in transmission potential appears to differ with R. rattus showing signs of lower susceptibility. These results provide further evidence that a multi-host reservoir is responsible for maintaining transmission with a bridge between infectious sylvatic and peridomestic rodent populations.