The objective was to clarify the impact of replacing cottonseed meal with canola meal (CM) on growth performance, blood metabolites, thyroxin function, and ruminal parameters of growing lambs. Twenty-four growing Barki male lambs (4–5 months of age) were assigned randomly into four equal groups (6 lambs each). Four dietary treatments were the control group with 0% CM (CON) and three experimental groups where CM replaced 25% (CN1), 50% (CN2), and 75% (CN3) of cottonseed meal. There were no dietary effects (P > 0.05) on the lambs’ feed intake, average daily gain, and feed conversion ratio of the lambs. The dietary CM linearly decreased the concentrations of serum total proteins (P = 0.003), albumin (P = 0.010), globulin (P = 0.011), AST (P = 0.041), and urea (P = 0.001) in growing lambs. The levels of ALT and creatinine, however, were not significantly affected by dietary treatments (P > 0.05). Furthermore, serum triiodothyronine, thyroxine, and electrolyte concentrations were similar (P > 0.05) in different dietary groups. Dietary treatments significantly affected the values of ruminal pH and ammonia at 0 h (P = 0.003 and 0.048, respectively) and 3 h (P = 0.033 and P = 0.006, respectively) postfeeding. The CN3 group showed significantly higher concentrations of ruminal ammonia at 0 and 3 h postfeeding. Furthermore, dietary CM (CN3) significantly reduced the ruminal pH values at 0 and 3 h postfeeding. Meanwhile, dietary treatments did not affect the concentration of total VFAs in the ruminal fluid. In conclusion, CM can replace the cottonseed meal (up to 75%) in lamb diets without compromising their growth performance, thyroid function, and ruminal fermentation parameters.