Anthropogenic climate change is linked to food web and salinity fluctuations in estuarine environments. Both decreased nutritional status and environmental salinity influence the physiological tolerance and health of fish populations; however, limited information on the interaction of these two factors and their physiological consequences is available. The green sturgeon (Acipenser medirostris) is a species of special concern in California, and the southern distinct population segment is listed as threatened. To test the hypothesis that poor nutrition negatively affects osmoregulation, juvenile green sturgeon (222 d posthatch) were randomly assigned to four feed restriction groups (12.5%, 25%, 50%, and 100% of the optimal feeding rate for 4 wk). Fish were then acutely exposed to 0-, 8-, 16-, or 32-ppt salinities and sampled at three time points (12, 72, or 120 h). Feed restriction significantly (P < 0.05) decreased specific growth rate, feed efficiency, condition factor, whole-body lipids, and protein content as well as plasma glucose, triglycerides, and proteins. Furthermore, feed restriction, salinity concentration, and salinity exposure time had significant effects on hematological indexes (hematocrit, hemoglobin), plasma values (osmolality, Na(+), K(+), Cl(-), glucose, lactate, cortisol), enzymatic activity (gill and pyloric ceca Na(+)/K(+) ATPase), and morphology of gill mitochondria-rich cells. The largest disturbances were observed at the highest salinity treatments across all feeding regimes. In addition, the interaction between feed restriction and acute salinity exposure at the highest salinity treatment resulted in high mortality rates during the first 72 h of salinity exposure. Evaluating the interactions of these environmental stressors and their implications on green sturgeon physiological tolerance will inform restoration and management efforts in rapidly changing estuarine environments.