Coastal estuaries are among the most heavily impacted ecosystems worldwide with many keystone fauna critically endangered. The delta smelt (Hypomesus transpacificus) is an endangered pelagic fish species endemic to the Sacramento-San Joaquin Estuary in northern California, and is considered as an indicator species for ecosystem health. This ecosystem is characterized by tidal and seasonal gradients in water parameters (e.g., salinity, temperature, and turbidity), but is also subject to altered water-flow regimes due to water extraction. In this study, we evaluated the effects of turbidity and salinity on feeding performance and the stress response of delta smelt because both of these parameters are influenced by water flows through the San Francisco Bay Delta (SFBD) and are known to be of critical importance to the completion of the delta smelt's life cycle. Juvenile delta smelt were exposed to a matrix of turbidities and salinities ranging from 5 to 250 nephelometric turbidity units (NTUs) and 0.2 to 15 parts per thousand (ppt), respectively, for 2 h. Best statistical models using Akaike's Information Criterion supported that increasing turbidities resulted in reduced feeding rates, especially at 250 NTU. In contrast, best explanatory models for gene transcription of sodium-potassium-ATPase (Na/K-ATPase)-an indicator of osmoregulatory stress, hypothalamic pro-opiomelanocortin-a precursor protein to adrenocorticotropic hormone (expressed in response to biological stress), and whole-body cortisol were affected by salinity alone. Only transcription of glutathione-S-transferase, a phase II detoxification enzyme that protects cells against reactive oxygen species, was affected by both salinity and turbidity. Taken together, these data suggest that turbidity is an important determinant of feeding, whereas salinity is an important abiotic factor influencing the cellular stress response in delta smelt. Our data support habitat association studies that have shown greater delta smelt abundances in the low-salinity zone (0.5-6.0 ppt) of San Francisco Bay, a zone that is also understood to have optimal turbidities. By determining the responses of juvenile delta smelt to key abiotic factors, we hope to aid resource managers in making informed decisions in support of delta smelt conservation.