Freshwater pearl mussels (FPMs, Margaritifera margaritifera, Linnaeus, 1758) are endangered and particularly vulnerable to climate change. To create effective conservation strategies, we studied their thermal tolerance and the impact of elevated water temperatures on growth and survival. Our experiments included field mesocosm studies in five FPM-streams in the Vogtland region (Germany) (2016 to 2020), as well as laboratory experiments at temperatures ranging from 1 to 26 °C. Growth of juvenile FPMs increased significantly within a temperature gradient from 12 to 21 °C. In the streams, maximum growth was 8.9 µm/d in surface water and 6.5 µm/d in the interstitial. The upper thermal tolerance for the mussels ranged from 22.1 to 22.9 °C, resulting in low survival during hot summer periods in 2018 and 2019. Warming during winter (+5 °C) did not significantly affect growth and survival, but survival during winter increased with the pre-overwintering shell length. Exceeding a shell length of about 1100 µm in December indicating gill development corelated to 50% survival. Shell length in December is primarily controlled by growth depending on water temperatures during summer. These findings define the thermal niche of juvenile FPMs (average summer temperatures of 14.5–21 °C) and have implications for water management, conservation strategies, and site selection for releasing captive-breeding mussels.