Salmon in the Klamath River of northern California contend with water temperatures that reach stressful and sometimes lethal levels during summer, forcing them to seek thermal refuge at coolwater tributary junctions. During migration, these fish also encounter a range of pathogens that affect their survival. A significant myxozoan parasite, Ceratonova shasta, causes enteronecrosis in salmon, and this disease increases in severity as temperature and parasite dose increase. In complementary laboratory and field studies, we examined how the use of a thermal refuge (an area at least 2°C colder than the main stem) affects progression of enteronecrosis in juvenile Chinook Salmon Oncorhynchus tshawytscha and Coho Salmon O. kisutch. We compared fish use, water temperature, and C. shasta concentration in a refuge at the Beaver Creek–Klamath River confluence during the summer in 2008 and 2010. Salmonid numbers ranged from 190 to 2,125, and temperatures were 2–8°C cooler than in the main stem. In June and July of 2008, parasite levels in the refuge were lower than in the main stem, where they exceeded 100 spores/L. In 2010, main‐stem parasite levels did not exceed 10 spores/L, and levels in the refuge were lower in June. In the laboratory, we compared the effect of fluctuating and constant temperature treatments on mortality rates of Chinook Salmon and Coho Salmon exposed to C. shasta. Under most experimental conditions, fluctuating temperature, within the range experienced by fish using thermal refuges (15.5–21°C), had no significant effect on disease progression compared with a constant midrange temperature (18.5°C) with equivalent degree‐day accumulation. We propose that in the Klamath River thermal refuges can function as disease refuges from enteronecrosis by (1) providing areas of decreased C. shasta exposure and/or (2) alleviating disease effects as a result of relatively lower water temperatures. The trend of increasing water temperatures suggests that juvenile salmon will rely even more on these critical habitats in the future.Received October 9, 2015; accepted February 25, 2016 Published online June 22, 2016