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Cisco (Coregonus artedi) are an important indicator species for cold-water lake habitats in the Great Lakes region, and many populations have been extirpated at their southern range limit over the last century. Understanding the roles of climate and water quality in these extirpations should inform protection of cold-water fishes. Using the water temperature at the depth where dissolved oxygen falls to 3mgL(-1) (TDO3) as a metric, we investigated the roles of climate and water quality as drivers of habitat availability for cisco in Lake Mendota, WI, USA from 1976 to 2013. We find that summer (Jun-Aug) air temperatures, spring (Mar-May) phosphorus load, and spring inflow influence summer TDO3. Warm air temperatures lead to the greatest increases in TDO3, whereas reduced phosphorus loads can reduce TDO3, thus alleviating oxythermal stress. Under air temperatures expected under the A1B climate change scenario, a 25% reduction in phosphorus load would stabilize TDO3 at current levels, while a 75% reduction in phosphorus loading would be required to expand oxythermal habitat. Costs of these reductions are estimated to range from US$16.9 million (-25%) to US$155-167 million (-75%) over a 20-year period but may be feasible by expanding upon current watershed phosphorus reduction initiatives if sustained funding were available. Identifying targeted reductions will become increasingly important throughout the region as warmer temperatures and longer stratification reduces cool- and cold-water fish habitat in many Midwestern lakes under the expected future climate.