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Low dissolved oxygen concentrations have resulted in nonsupport of the aquatic recreation use in Upper Oyster Creek in southeast Texas. The studied reach of Upper Oyster Creek did not meet the24-hour minimum dissolved oxygen criterion, which is generally a symptom of nutrient enrichment and perhaps hydrologic modifications. The QUAL2K model was applied to investigate dissolved oxygen processes in the study reach due to its capability to simulate diel dissolved oxygen fluctuations. The QUAL2K model was calibrated and then verified using two time periods of intensive monitoring data. The calibrated and verified model performed well in simulating water quality constituents including nutrients, carbonaceous biochemical oxygen demand, benthic algae, phytoplankton, and the key state variable of dissolved oxygen, indicating that QUAL2K was capable of simulating dissolved oxygen in Upper Oyster Creek. The model can now be used to investigate various conditions and changes that affect dissolved oxygen for the purpose of determining control measures that can reduce the dissolved oxygen impairment in Upper Oyster Creek. In addition, a sensitivity analysis indicated that reaeration and sediment oxygen demand rates, maximum growth rates of phytoplankton and benthic algae, and CBOD and NH3-N parameters had impacts on dissolved oxygen in a sequence of highest to lowest sensitivity.