This study evaluated the effects of dietary supplementation with free- or nano-curcumin on the growth performance, immune status and heat stress resistance of Nile tilapia (Oreochromis niloticus). Seven isonitrogenous (28% protein) and isocaloric (445 kcal/100 g DM) diets were prepared. Six diets were supplemented with three levels of nano-curcumin (50 (CN50), 100 (CN100), 200 (CN200) mg kg⁻¹diet) or free-curcumin (50 (C50), 100 (C100), 200 (C200) mg kg⁻¹diet), and the control diet was left without an additive (CON). Fish (13.54 ± 0.32 g) (mean ± SD) fed the experimental diets for 65 days. Following the feeding trial, the fish were exposed to the acute heat stress by gradually raising the water temperature from 25 to 40 °C within 3 h. The fish were then exposed to 40 °C for 4 h. Results revealed the superiority of nano-curcumin over its free-form in enhancing the growth performance, with the highest results obtained at CN100, followed by CN200. Only heat stress, not the experimental diets, increased the platelets, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), leukocytes and neutrophils count, while lymphocytes decreased. The CN50 and CN100 groups showed lower activity of liver enzymes (alanine aminotransferase (ALT) and aspartate aminotransferase (AST)) than the other treatments, while C200 gave the highest activity of these enzymes. The highest immunoglobulin (IgM) levels were detected in CN100, CN200, C100 and C200, followed by CN50. The C200 group showed higher levels of complement 3 and complement 4 (C3 and C4, respectively) than the other treatments. The C50 and CON groups gave the lowest values of IgM, C3 and C4. Cortisol levels were significantly lower in the CN50 and CN100 groups compared to the other groups. After the heat stress, ALT, AST, IgM, C3, C4, cortisol and glucose increased. Thus, nano-curcumin is more effective than its free-form in enhancing the resistance to heat stress, inducing innate immunity, lowering the stress indicators and promoting growth performance of Nile tilapia with the best concentration at 100 mg kg⁻¹diet.