Native freshwater mussels are a diverse but imperiled fauna and may be especially sensitive to increasing water temperatures because many species already may be living near their upper thermal limits. We tested the hypothesis that elevated water temperatures (20, 25, 30, and 35°C) adversely affected the survival and physiology of 2-mo-old juvenile mussels (Lampsilis abrupta, Lampsilis siliquoidea, and Megalonaias nervosa) in 28-d laboratory experiments. The 28-d LT50s (lethal temperature affecting 50% of the population) ranged from 25.3 to 30.3°C across species, and were lowest for L. abrupta and L. siliquoidea. Heart rate of L. siliquoidea was not affected by temperature, but heart rate declined at higher temperatures in L. abrupta and M. nervosa. However, for both of these species, heart rate also declined steadily during the experiment and a strong temperature × time interaction was detected. Juvenile growth was low for all species in all treatments and did not respond directly to temperature, but growth of some species responded to a temperature × time interaction. Responses to thermal stress differed among species, but potential laboratory artifacts may limit applicability of these results to real-world situations. Environmentally relevant estimates of upper thermal tolerances in native mussels are urgently needed to assess the extent of assemblage changes that can be expected in response to global climate change.