In Caspian Sea basin, sturgeons spend the larval and juvenile stages in freshwaters of rivers and then, they migrate to brackish waters of the sea where they grow and mature. With regard to the elevation of the metal concentrations in coastal waters and sediments of the Caspian Sea and its adjacent rivers, it is likely that juvenile sturgeon are exposed to sub-lethal levels of metals during seawater entry process. We compared the biochemical responses of juvenile European sturgeon, (Beluga, Huso huso) exposed to a sub-lethal level of copper (Cu, 20 μg/L) and cadmium (Cd, 300 μg/L) in freshwater (FW, 0 ppt) and brackish water (BW, 11 ppt) for seven days. The results showed that the levels of plasma glucose increased significantly in BW and in all metal exposed groups. Also, plasma cortisol concentrations showed significant increases when juveniles were exposed to BW, Cu(FW/BW) and Cd(BW). The activity of liver superoxide dismutase (SOD) decreased significantly in BW compared with FW. Moreover, Cu and Cd exposure enhanced the activity of SOD in BW, while SOD did not show any changes in FW. The levels of tissue and plasma proteins as well as plasma triiodothyronine (T3), thyroxine (T4) and liver Catalase (CAT) activity remained constant when animals were exposed to Cu/Cd in both FW and BW environments. Our data indicate that exposure of juvenile beluga to BW stimulated the general biochemical responses of stress such as cortisol and glucose, while sub-lethal exposure to Cu and Cd caused oxidative stress in BW environment but not in FW.