Seasonal changes of trace elements, nutrients, dissolved organic matter (DOM), and carbonate system parameters were evaluated over the largest deteriorating oyster reef in the Western Mississippi Sound using data collected during spring, summer, and winter of 2018, and summer of 2019. Higher concentrations of Pb (224%), Cu (211%), Zn (2400%), and Ca (240%) were observed during winter of 2018 compared to summer 2019. Phosphate and ammonia concentrations were higher (> 800%) during both summers of 2018 and 2019 than winter of 2018. Among the three distinct DOM components identified, two terrestrial humic-like components were more abundant during both spring (12% and 36%) and summer (11% and 33%) of 2018 than winter of 2018, implying a relatively lesser supply of humic-like components from terrestrial sources during winter. On the other hand, the protein-like component was more abundant during summer of 2019 compared to rest of the study period, suggesting a higher rate of autochthonous production during summer 2019. In addition, to their significant depth-wise variation, ocean acidification parameters including pH, pCO(2), CO32-, and carbonate saturation states were all higher during both summers of 2018 and 2019. The measured variables such as trace elements, organic carbon, suspended particulates, and acidification parameters exhibited conservative mixing behavior against salinity. These observations have strong implications for the health of the oyster reefs, which provides ecologically important habitats and supports the economy of the Gulf Coast.