Tiger muskellunge (the F1 hybrid of female muskellunge Esox masquinongy and male northern pike E. lucius) have survived poorly when stocked in reservoirs. To understand why, we quantified, in the laboratory, both mortality and plasma glucose responses to three common stocking stressors: Dipnet handling, confinement, and temperature increase. No young‐of‐year hybrids died within 48 h when the temperature was abruptly increased 10°C and only 5% died when the temperature was increased 12°C, but 98% died within 4 h when the temperature was increased 15°C. Thus, we concluded that thermal stress is an important determinant of post-stocking mortality. Mortalities in response to three multiple‐stressor treatments–(1) handling and temperature increase, (2) handling, confinement at a fish density of 83 g/L, and temperature increase, and (3) handling, confinement at 135 g/L, and temperature increase–did not differ from each other or from mortality associated with a temperature increase alone. Thus, handling and moderate‐density confinement during transport do not necessarily increase post-stocking mortality of tiger muskellunge. Abrupt temperature increases of 12 and 15°C increased peak plasma glucose concentrations significantly. Handling and confinement together caused a significant hyperglycemia both with and without a temperature increase. However, the relative magnitude of the hyperglycemia caused by individual handling and confinement stressors depended on the presence of a thermal stressor. Finally, we found that plasma glucose concentrations and mortality were not correlated. Although glucose is easily measured and sensitive to small changes in stress, it is not a good indicator of reduced survival and should not be used as such in studies intended to quantify stress‐induced mortality.