Degraded water quality may affect recruitment of juveniles to populations of shortnose sturgeon, Acipenser brevirostrum, in the southeastern United States. However, field data for young-of-the-year (YOY) shortnose sturgeon are limited. Therefore, little information exists about the physiological capabilities of YOY shortnose sturgeon. I conducted LC50, factorial, and thermal maxima experiments to examine ontogenetic changes in salinity and temperature tolerances of YOY shortnose sturgeon. In LC50 experiments, salinity and temperature tolerances increased with increasing size. Results of factorial experiments were used to generate a predictive survival model based on salinity (ppt), temperature (C), and weight (g). Plasma osmolalities and hematocrit values of survivors indicated significant sublethal effects of salinity and temperature (p < 0.0001). Thermal maxima experiments demonstrated that acclimation temperature significantly affected temperature tolerances (p < 0.0001). Results can be used to identify critical YOY habitats and mitigate further disturbances to rivers in the southeastern United States.