This study investigates factors influencing stratification and dissolved oxygen (DO) in the Upper Gulf of Thailand (UGoT). Major rivers flowing into the gulf introduce freshwater and creates conditions conducive to stratification leading to distinct zones with varying temperature, salinity, and DO. The halocline, the boundary between freshwater and saltwater layers, acts as a barrier to mixing and reinforces stratification. In areas with strong stratification, hypoxia (low oxygen condition) and anoxia (no oxygen condition) can occur in the deeper layers, leading to the death of marine organisms and aquaculture species. Data analysis from a telemetry marine measurement station, GOT001, located in the eastern side of UGOT, reveals significant fluctuations in DO potentially controlled by numerous factors. Particularly during July-September, DO concentrations often exceed 8 mg/l in the daytime and fall below 1 mg/l at night. To understand the complex interplay of factors driving DO fluctuations, a three-dimensional hydrodynamic and water quality model was developed for the entire UGoT. Different model scenarios were investigated to elucidate the influence of individual factor on the DO dynamics. Preliminary results suggest that both biological, chemical and physical processes contribute to these fluctuations. Biological factors (notably phytoplankton blooms and biomass decomposition) and chemical factor (i.e., riverine nutrient fluxes), are among the most important factors. Physical processes, including tidal currents, wind patterns, and stratification by river water, also are crucial factors. To this end, we posit that this understanding is essential for developing effective strategies to manage water quality and protect marine ecosystems in the UGOT and perhaps similar systems in this region.