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During the 20th century, there has been an ongoing agricultural expansion and global warming, two of the main determinants influencing biodiversity changes in Argentina. The red hocicudo mouse (Oxymycterus rufus) inhabits subtropical grasslands and riparian habitats and has increased its abundance in recent years in central Argentina agroecosystems. This paper describes the long‐term temporal changes in O. rufus abundance in Exaltación de la Cruz department, Buenos Aires province, Argentina, in relation to weather fluctuations and landscape features, as well as analyzes the spatio‐temporal structure of captures of animals. We used generalized liner models, semivariograms, the Mantel test, and autocorrelation functions for the analysis of rodent data obtained from trappings conducted between 1984 and 2014. O. rufus showed an increase in abundance across the years of study, with its distribution depending on landscape features, such as habitat types and the distance to floodplains. Capture rates showed a spatio‐temporal aggregation, suggesting expansion from previously occupied sites. O. rufus was more abundant at lower minimum temperatures in summer, higher precipitation in spring and summer, and lower precipitations in winter. Weather conditions affected O. rufus abundance, but there was local variation that differed from global patterns of climate change. [ABSTRACT FROM AUTHOR]