The dissolved oxygen concentrations (DO) were measured during four expeditions between 2007 and 2008 in the Sangga Besar River Estuary in the Matang Mangrove Forest Reserve (MMFR), Peninsular Malaysia. Hypoxic conditions (DO < 3 mg/L) were observed during periods of well mixed spring tides almost throughout the estuary, while in the partially stratified neap tides, hypoxia in the estuary was restricted to the upper river and subsurface layers in the branch and creek area, where high Acid Volatile Sulfide and low oxidation-reduction potential values were observed in the surface sediments due to the accumulation and decomposition of mangrove derivedorganic matter. Basedonthe δ¹³C, the contribution of mangrove derived organic matter in the surface sediments of the creek area was estimated to be 77-87%. While in the coastal area, the contribution of phytoplankton was 58-68%. These results indicate that the formation of hypoxic waters in the estuary is mainly due to the tidal mixing of hypoxic waters from the creeks and branches with the estuarine waters during spring tides and probably oxygen consumption by resuspended sediments.