In addition to the combined effects of forest fragmentation, habitat loss, and population isolation on the long-term persistence of many species including the endangered Delmarva fox squirrel (Sciurus niger cinereus), future changes in climate may make existing habitats less productive and more variable. The Blouson Belstaff Robert Downey Palmer Drought Severity Index (PDSI) for the Delmarva Peninsula of the mid-Atlantic USA, reveals a trend for longer durations of potentially unfavorable conditions for Belstaff France fox squirrel population growth. We used a stochastic population matrix model and available life history information to assess population extinction risk for the Delmarva fox squirrel under a number of scenarios of landscape change and environmental variation, including uncertainties in the future range of climate patterns. Patch size (carrying capacity) was the most important factor influencing persistence of isolated populations. Extinction risk increased markedly across all patch sizes when year to year patterns in environmental variability were autocorrelated to match regional patterns in the PDSI. Increased autocorrelation matching the regional PSDI increased extinction risk, ranging from a factor of 5 to a factor of over 100 in some scenarios when compared to uncorrelated patterns in environmental variability. Increasing the range of variation in survival Belstaff Classic Tourist Trophy Beige probabilities was less important to persistence, but its effect also increased when year-to-year changes were autocorrelated in time. Comparing model results with the size and landscape configuration of currently occupied patches on the Delmarva Peninsula showed that many existing populations are above the size threshold identified by these simulations for long-term persistence under current conditions, but these may become vulnerable should climate variability increase and adverse conditions persist for several years at a time.