Simple SummaryClimate warming is evident at many cold sites, including high-altitude and high-latitude lakes. The cladoceran Daphnia pulex, with high calcium (Ca) demands for its heavily calcified exoskeleton, is an ecologically important zooplankton species inhabiting these lakes, many of which are Ca-limited. Other stressors, such as warming and food limitation, may interact with Ca limitation and affect Daphnia populations adapted to these cold environments. In a study of factorial design, a clone of North American Daphnia cf. pulex was exposed to a low-Ca gradient, to temperature rises within its preferred range and expected in these lakes, and to conditions of low and high food quantity. Results suggest that climate warming and higher food availability will make D. pulex populations more tolerant to Ca limitation. Changes in the abundance of Daphnia may be relevant to ecological processes and the functioning of aquatic ecosystems.Calcium (Ca) is an important driver of community structure in freshwaters. We examined the combined effects of increased temperatures and variations in food quantity on the tolerance to low Ca of Daphnia pulex. The aim was to predict the impact of climate warming on this keystone zooplanktonic species in cold-climate lakes. We conducted a factorial life-history experiment in a clone of North American Daphnia cf. pulex to analyse the interaction effects of a temperature increase (17.5 °C–21 °C) within their physiological preferred range and expected by climate warming over the next few decades and a narrow Ca gradient (0.25–1.74 mg Ca L−1) under stressful vs. abundant food conditions. We found a striking positive synergistic effect of Ca and temperature on D. pulex reproduction at high food conditions. Although the increase in temperature to 21 °C greatly reduced survival, high energy allocation to reproduction at high food levels allowed the population to succeed in poor Ca (<0.25 mg Ca L−1). Results suggest that climate warming and higher food availability will make the populations of many cold and Ca-limited lakes more tolerant to low Ca levels with higher growth population rates, thereby altering zooplanktonic community structures and inducing potential cascading effects on the food web.