The Gulf of Lions is a river-dominated ocean margin that receives high loads of nutrients and particulate matter from the Rhône River but most particulate materials settle rapidly on the nearshore seafloor. One question is raised on the fate of these large quantities of organic carbon delivered by the river to the coastal marine environment. Surface sediments (0–0.5 cm) were collected in the Rhône prodelta and its adjacent shelf during a period of low river discharge (April 2007, 16 stations). The sources, distribution and lability of sedimentary organic matter were examined using bulk (organic carbon, total nitrogen, stable carbon isotope ratios, and grain size) and molecular-level (pigments, amino acids, fatty acids, and δ13C of individual fatty acids) analyses. Our results confirmed previous observations of a southwestward Rhodanian imprint in the nearshore sediments, with 97% of terrigenous inputs of organic matter near the river mouth. Isotopic values of bulk organic carbon, as well as fatty acid biomarkers and compound-specific δ13C signatures of most fatty acids clearly indicate that the Rhône inputs consist of a mixture of organic matter (OM) from different origins with a strong contribution from terrestrial sources (soil and plant debris), and a smaller input from freshwater microalgae, mostly diatoms. The influence of the Rhône River was prominent within the first ten kilometers, but may still be observed on the outer shelf (~21 km) as indicated by the occurrence of long chain fatty acids, which are derived from vascular plants, and their δ13C signatures. In the proximal prodelta, bacteria-specific fatty acids were abundant (1.65 mg g−1 OC at the mouth site) and were relatively depleted in δ13C confirming that bacteria mostly utilize land-derived OM. In the shelf area, the inputs of marine OM and its predominant utilization by the bacteria was confirmed, but the coupling between the pelagic and the benthic compartments appeared limited at this period of the year. Overall, degradation indexes based on amino acids (Dauwe's degradation index) and pigments (ratio of intact chlorophyll-a to the sum of chlorophyll-a + phaeopigment-a), as well as isotopic enrichment of source-specific fatty acids reveal an offshore gradient of OM decay reflecting the rapid deposition of the terrestrial material in the prodelta, the low mixing with OM deriving from marine sources and the efficient degradation of the OM. The OM delivered by the Rhône is relatively labile based on the intermediary value of Dauwe's degradation index, the high proportion of bio-available nitrogen and the occurrence of polyunsaturated fatty acids. Deltaic sediments off the Rhône River should thus be of sufficiently high nutritional quality to sustain dense macrofaunal communities.