Three sediment cores were collected off the Mississippi River delta on the Louisiana Shelf at sites that are variably influenced by recurring, summer-time water-column hypoxia and fluvial loadings. The cores, with established chronology, were analyzed for their respective carbon, nitrogen, and sulfur elemental and isotopic composition to examine variable organic matter inputs, and to assess the sediment record for possible evidence of hypoxic events. Sediment from site MRJ03-3, which is located close to the Mississippi Canyon and generally not influenced by summer-time hypoxia, is typical of marine sediment in that it contains mostly marine algae and fine-grained material from the erosion of terrestrial C4 plants. Sediment from site MRJ03-2, located closer to the mouth of the Mississippi River and at the periphery of the hypoxic zone (annual recurrence of summer-time hypoxia >50%), is similar in composition to core MRJ03-3, but exhibits more isotopic and elemental variability down-core, suggesting that this site is more directly influenced by river discharge. Site MRJ03-5 is located in an area of recurring hypoxia (annual recurrence >75%), and is isotopically and elementally distinct from the other two cores. The carbon and nitrogen isotopic composition of this core prior to 1960 is similar to average particulate organic matter from the lower Mississippi River, and approaches the composition of C3 plants. This site likely receives a greater input of local terrestrial organic matter to the sediment. After 1960 and to the present, a gradual shift to higher values of δ¹³C and δ¹⁵N and lower C:N ratios suggests that algal input to these shelf sediments increased as a result of increased productivity and hypoxia. The values of C:S and δ³⁴S reflect site-specific processes that may be influenced by the higher likelihood of recurring seasonal hypoxia. In particular, the temporal variations in the C:S and δ³⁴S down-core are likely caused by changes in the rate of sulfate reduction, and hence the degree of hypoxia in the overlying water column. Based principally on the down-core C:N and C:S ratios and δ¹³C and δ³⁴S profiles, sites MRJ03-3 and MRJ03-2 generally reflect more marine organic matter inputs, while site MRJ03-5 appears to be more influenced by terrestrial deposition.