Dissolved organic matter (DOM) represents one of the largest exchangeable C reservoirs on earth. However, molecular level information of DOM remains elusive due to its chemical complexity and our technical limitation in characterization. In this study, natural DOM samples were collected from five South Texas rivers (Aransas, Lavaca, Mission, Nueces, and San Antonio Rivers) in summer (July) of 2016, and their molecular level changes through a microcosm incubation were investigated using high-resolution mass spectrometry: Ion Mobility Quadrupole Time Of Flight (Q-TOF) Liquid Chromatography Mass Spectrometry (IM QTOF LC/MS). The results showed that bioavailable DOC (BDOC) and bioavailable dissolved organic nitrogen (BDON) ranged from 0.3% to 6.1% and 8.6% to 15.1% respectively, with no significant difference among the five rivers. Liquid chromatography and high-resolution MS further revealed even though total DOC concentration did not change much throughout incubation, a significant shift in DOM community occurred. For instance, under ESI- mode, with many compounds disappearing through incubation, the averaged O/C ratio of the assigned formulas decreased while the H/C ratio increased, changing the DOM community to be more marine-like? This trend seems to be mostly driven by the disappearance of marine-like?compounds during the incubation. Geometric conformation and isomeric information of DOM were further investigated with the IM-MS function. Our data showed that natural DOM generally possess a more compacted geometric conformation compared with known standard biomolecules. Furthermore, geometric conformation of natural DOM did not present a significant change through the incubation. However, isomer percentage decreased from ca. 7% before incubation to ca. 4% after incubation, indicating that DOM community becomes more homogenous with incubation. The analysis is still on going, and more molecular-level data will be presented.