Gulf of Mexico saltmarsh sediments were heavily impacted by Macondo well oil (MWO) released from the 2010 Deepwater Horizon (DWH) oil spill. Detailed molecular-level characterization of sediment extracts collected over 48 months post-spill highlights the chemical complexity of highly polar, oxygen-containing compounds that remain environmentally persistent. Electrospray ionization (ESI) Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS), combined with chromatographic prefractionation, correlates bulk chemical properties to elemental compositions of oil-transformation products as a function of time. Carboxylic acid incorporation into parent MWO hydrocarbons detected in sediment extracts (corrected for mass loss relative to C30 hopane) proceeds with an increase of ∼3-fold in O2 species after 9 months to a maximum of a ∼5.5-fold increase after 36 months, compared to the parent MWO. More importantly, higher-order oxygenated compounds (O4-O6) not detected in the parent MWO increase in relative abundance with time as lower-order oxygenated species are transformed into highly polar, oxygen-containing compounds (Ox, where x > 3). Here, we present the first molecular-level characterization of temporal compositional changes that occur in Deepwater Horizon derived oil contamination deposited in a saltmarsh ecosystem from 9 to 48 months post-spill and identify highly oxidized Macondo well oil compounds that are not detectable by routine gas-chromatography-based techniques.