Bivalve shellfish perform numerous ecosystem services but are under threat from a variety of stressors. Climate change will alter the environmental conditions that bivalve shellfish are sensitive to, so restoration efforts should consider how the future climate will evolve. Here, climate model projections and statistical water quality models were used to estimate future changes in temperature, salinity, dissolved oxygen, and pH in the tidal freshwater region of the Delaware Estuary that are expected to result from increases in greenhouse gases and the associated climate change. Projections from eight regional climate models utilizing a medium-high emissions scenario were presented for the time period 2041-2070 during the summer, when bivalve growth rates are highest. Water temperature throughout the tidal freshwater region is expected to increase by 2.7 to 3.5 °C (95% confidence range). Near Reedy Island, where the current annual mean salinity is 4.4, salinity is expected to increase by 1.1 to 2.1 in summer as a result of streamflow declines and sea-level rise. However, in most of the tidal freshwater region, which is just upstream of Reedy Island, mean salinity change is expected to be very small, with the mean position of the 0.5 isohaline (which defines the seaward extent of the tidal freshwater region) projected to move landward by only 4 km. The combined effects of a decrease in solubility and an increase in respiration (both resulting from warming) lead to an oxygen concentration decrease of about 20 mmol m-3 near Ben Franklin Bridge (the site of the lowest oxygen concentrations), which is a decline of approximately 13%. pH is expected to decline by 0.08 as a result of increased temperature, respiration, and atmospheric CO2. The projected changes are expected have negative impacts on bivalves in the region, preferentially natives. The greatest concern regards the oxygen decline, which will increase the hypoxic stress that bivalves are currently experiencing during summer. Future research should consider changes in variability (e.g., changes in drought frequency and tidal range) as well as laboratory and field experiments to better quantify the impact of environmental conditions on bivalves in the tidal freshwater region.