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This study was aimed to investigate the Cu bioavailability, growth response, digestibility of nutrients, and blood metabolites of broiler chicks fed CuSO4 in nano or common forms. A total of 720 broiler chickens were distributed between eight treatments according to a completely randomized design. There were 8 treatments and 6 replicates in each treatment with 15 birds/replicate. The treatments were divided into common copper sulfate at the doses of 16 ppm, 40 ppm, 80 ppm, and 120 ppm (INO) and hot-melt extruded copper sulfate at the doses of 16 ppm, 40 ppm, 80 ppm, and 120 ppm (HME-Cu). The experiment was operated for 35 days in 2 phases (phase 1, d 0 to 14; and phase 2, d 15 to 35). No significant differences were shown in growth performance, feed intake, FCR, and nutrient digestibility among the treatments. The concentration of Cu in the serum was increased in the HME-Cu broilers compared with the INO broilers at phase 2. A linear increase was observed in the concentration of Cu in the liver in broilers fed INO diets, however, no significant differences were observed by the supplementation of HME-Cu levels. The linear increase was detected in the content of Cu in excreta in the INO and HME-Cu treatments by increasing the dietary Cu content. The HME-Cu treatments showed a lower Cu concentration in the excreta compared with the INO treatments. The higher bioavailability of Cu in HME form can decrease the recommended dose of Cu in broiler diets.