Sodium bicarbonate (NaHCO₃) is the principal salt in coal bed natural gas produced water from the Powder River Structural Basin, Wyoming, USA, and concentrations of up to 3000 mg NaHCO₃/L have been documented at some locations. No adequate studies have been performed to assess the chronic effects of NaHCO₃ exposure. The present study was initiated to investigate the chronic toxicity and define sublethal effects at the individual organism level to explain the mechanisms of NaHCO₃ toxicity. Three chronic experiments were completed with fathead minnows (Pimephales promelas), 1 with white suckers (Catostomus commersoni), 1 with Ceriodaphnia dubia, and 1 with a freshwater mussel, (Lampsilis siliquoidea). The data demonstrated that approximately 500 mg NaHCO₃/L to 1000 mg NaHCO₃/L affected all species of experimental aquatic animals in chronic exposure conditions. Freshwater mussels were the least sensitive to NaHCO₃ exposure, with a 10-d inhibition concentration that affects 20% of the sample population (IC20) of 952 mg NaHCO₃/L. The IC20 for C. dubia was the smallest, at 359 mg NaHCO₃/L. A significant decrease in sodium–potassium adenosine triphosphatase (Na⁺/K⁺ ATPase) together with the lack of growth effects suggests that Na⁺/K⁺ ATPase activity was shut down before the onset of death. Several histological anomalies, including increased incidence of necrotic cells, suggested that fish were adversely affected as a result of exposure to >450 mg NaHCO₃/L.