Stress can unfavorably affect fish health in hatcheries and it is important to understand how different stressors can change stress response. Dexamethasone (DEX), a synthetic glucocorticoid hormone, shows biological effects in response to stressor conditions. This study was performed to examine the effect of intraperitoneal injection of DEX on the stress response of Siberian sturgeon (Acipenser baerii), an important chondrostean species for aquaculture. For this purpose, one hundred juvenile Siberian sturgeon (average weight 279.0 ± 46.1 g [mean ±SD]) were distributed in two treatments: (1) DEX (1 mg DEX kg −1 body weight) and (2) physiological saline solution as control. 2-min air exposure was applied as an acute stressor. Blood samples were taken before injection and 0.5, 1, 2, 3, 6, 12 and 24 h post-stress. Cortisol levels showed an increasing trend in control treatment and a significant difference was found between control and DEX-treated fish. The highest levels of cortisol in DEX treatment (40.6 ± 0.4 ng mL −1 ) was recorded at 0.5 h after stress, then showed a decline and finally reached to basal level (24.2 ± 0.7 ng mL −1 ) at 24 h. The highest glucose (118.0 ± 2.9 mg dL −1 ) and lactate (125.0 ± 20.8 mg dL −1 ) values was found at 3 h post-stress in DEX-treated sturgeon and showed significant difference compared with control treatment (glucose: 84.5 ± 2.6 mg dL −1 and lactate: 56.8 ± 17.9 mg dL −1 ).After 24 h, glucose and lactate concentrations were returned to the basal level in both treatments. Our results showed that the injection of 1 mg DEX kg −1 BW to Siberian sturgeon has a potent role on stress response and describe an inhibitory effect on plasma cortisol following acute stress under laboratory condition.