Coproducts from the production of fuel ethanol may have the potential to be used as protein sources for Rainbow Trout Oncorhynchus mykiss if dietary supplementation strategies that can maintain fish performance can be identified. A random sample of one such coproduct, grain distiller's dried yeast (GDDY), contained detectable levels of ochratoxin A, deoxynivalenol, zearalenone, fumonsin B1, and fumonsin B3. Therefore, the goal of this study was to test whether growth performance of Rainbow Trout fed GDDY could be improved by dietary supplementation of a mycotoxin deactivator (Mycofix Plus). The study was conducted as a 2 × 3 factorial design in which there were two levels of mycotoxin deactivator (0.1% or 0%) and three levels of GDDY inclusion (0, 15, and 30%). All diets were formulated to include 42% digestible protein and 20% crude lipid and were balanced for lysine, methionine, threonine, and total phosphorus. Juvenile Rainbow Trout (average initial body weight, 26.4 ± 0.9 g [mean ± SD]) were stocked at 15 fish per tank, three replicates per diet, and were fed twice daily for 12 weeks. Grain distiller's dried yeast inclusion at 15% and 30% of the diet reduced the growth of Rainbow Trout (P = 0.0010). In contrast, no significant differences in feed intake and feed conversion ratio (FCR) were observed for Rainbow Trout fed diets having the 0% and 15% GDDY inclusion levels. However, increased feed intake (P = 0.0002) and FCR (P = 0.0002) were observed in Rainbow Trout fed the 30% GDDY diet. Only minor trends of increased fish growth (P = 0.0773) and protein (P = 0.0527) and energy (P = 0.0538) retention were observed when mycotoxin deactivator was supplemented regardless of yeast inclusion. These results suggest that there are minor benefits of myctoxin deactivator supplementation to Rainbow Trout diets where mycotoxin contamination may be suspected but was independent of GDDY inclusion level.