The objectives of this study were to investigate the role that fauna play in short-term OM processing, how this varies with OM supply and quality, oxygen availability and faunal community structure, and how faunal activity is linked to sediment organic geochemistry. This was achieved through experiments and organic geochemical sampling, at sites spanning the OMZ on the Pakistan margin. The steep gradients in OM quantity and quality, oxygen, and faunal communities, and seasonal changes in OM supply, provided an exceptional natural setting to assess these relationships. Incubation studies were conducted on intact sediments containing whole faunal communities, aboard ship and in situ and using a novel system to maintain ambient oxygen levels. ¹³C-labelled algae were added to the sediments and traced into organisms, sediments, and respired pools. The resulting carbon budgets are some of the most complete to date, and allowed direct comparison among an unprecedented range of site conditions. Where macrofauna and higher-quality OM were present, OM uptake by fauna was greater; at one site macrofaunal uptake equalled total respiration, illustrating the key significance of fauna. Oxygen had a threshold effect on the faunal groups responsible for OM processing, with foraminifera and macrofauna dominating OM processing below and above the threshold, respectively. Notably, a new technique was developed for the quantitative tracing of labelled amino acids, which allowed the first molecular level tracing of OM in whole community and in situ experiments, and provided among the first direct links between faunal digestive activity and sediment OM composition. Compound-selective assimilation and OM alteration were observed, the patterns of which were taxon-specific.