The round-tailed muskrat (Neofiber alleni) is a species of conservation concern that represents a monotypic genus with a restricted geographic distribution. Few data exist on space use to assist conservation efforts for this enigmatic species. We radiotracked 23 round-tailed muskrats in isolated freshwater wetlands in central Florida. Muskrats used lodges for diurnal rest sites when wetlands were inundated but switched to burrows during a seasonal dry period. Individuals shifted use among 10–15 rest sites within their home ranges. Body mass affected patterns of rest-site use; heavier individuals used fewer rest sites and were more likely to have a preferred site compared to lighter individuals. Estimates of home-range size averaged 1,263–2,071 m² and were at least an order of magnitude greater than existing estimates but less than expected given the body size of the species. Males may sometimes occupy nonoverlapping home ranges as predicted by theory. Small wetlands can support subpopulations of the round-tailed muskrat, which is a dispersal-limited species that exhibits metapopulation dynamics among wetlands.