The genera Oryctolagus and Lepus (order Lagomorpha) are essential elements in the trophic chain in the Iberian Peninsula, being the main prey of many predators, including some highly endangered predators such as the Iberian lynx ( Lynx pardinus ). Myxomatosis, a disease producing tumorations in conjunctive tissues, and produced by the Myxoma Virus , has caused mass mortalities in rabbits ( Oryctolagus cuniculus ) for decades. Recently, the virus has jumped interspecifically from rabbits to hares, and this has created a depletion in hare populations, generating great concern. We analyzed the population dynamics and distribution of both lagomorph species in a Mediterranean agricultural area of the south of Spain since the 1990s with a combination of systematic and non-systematic data. The appearance of the outbreak in the Iberian hare ( Lepus granatenis ) in 2018 enabled us to undertake an opportunistic analysis of its effects on the spatial structure and assemblages, as well as on the niches of both species using PCA analyses and ordination techniques. Analysis of the mortality effect on daily and seasonal cycles was also conducted, and relations with the temporal dimension was tested using generalized lineal models (GLMs). In our results, in addition to population and temporal patterns, we could observe a restructuring in hare distribution after the mortality event, highlighting that prior to the outbreak, rabbit and hare populations were spatially differentiated, although with some overlaps and niche similarities. However, since the outbreak, hare populations have been excluded from rabbit areas, suggesting that in the absence of rabbits, the virus has more difficulties to infect hares. We also provide an overview of the effect of this population depletion on the ecological and socio-economic dimension of this region, pointing out the importance of this situation for the area.