Hypoxia is increasing in coastal oceans. This is because eutrophication has increased oxygen consumption, while less oxygen is replenished to the bottom under stronger stratification. Quantifying these biogeochemical and physical drivers is important for management and predicting future trends. By using observations from the Pearl River Estuary (PRE) region (10-70 m deep) and similar coastal systems, this paper introduces a simple analysis to quantify both the biogeochemical and physical drivers of hypoxia. We show that in the PRE region, sediment respires >60% of organic matter produced in the water column, leading to high sediment oxygen uptake (average 41.1±16.3 mmol m-2 d-1) and shallow oxygen penetrations (2-7 mm). The sediment’s effect on the bottom oxygen loss becomes stronger with the reducing thickness of the bottom boundary layer. We then construct a generic mass-balance model to quantify oxygen loss, determine timescales of hypoxia formation, and explain within- and cross-system variabilities.