Lake Mathews is a large, oligo-mesotrophic reservoir located in Southern California. The reservoir has elevated levels of nitrate and periodically experiences hypolimnetic anoxia. Experimental sediment-water chamber incubations and reservoir water quality monitoring were conducted to evaluate how oxygen and nitrate in overlaying water affect nutrient release from profundal sediments and internal nutrient loading. In experimental incubations, under nitrate-free anoxic conditions, sediment nutrient release rates were 3.4 ± 0.8 mg-P/m2 ·d for phosphate and 2.8 ± 1.2 mg-N/m2 ·d for ammonia (average ± standard deviation; n = 6). Oxygen repressed phosphate release and greatly diminished ammonia release from sediments in experimental incubations while nitrate only repressed phosphate release. Similar nutrient release dynamics were observed in the reservoir. Nutrient release rates estimated from seasonal nutrient profiles collected from the reservoir were 3.4 mg-P/m2 ·d for phosphate and 2.5 mg-N/m2 ·d for ammonia. Ammonia accumulation in the hypolimnion commenced with the onset of anoxic conditions, but phosphate accumulation did not start until nitrate disappeared from bottom waters approximately 6 weeks later. The time lag decreased total internal phosphorus loading by approximately 25% relative to hypothetical nitrate-free conditions. Laboratory and field data show that both oxygen and nitrate repress sediment phosphate release, likely via the maintenance of an oxidized surficial sediment layer that retains phosphate in iron-oxide complexes. However, only oxygen and not nitrate was effective in decreasing sediment ammonia release, likely by enhancing biological nitrification and assimilation in surficial sediments under oxic conditions. A number of in-lake management strategies have been developed to inhibit internal nutrient loading including calcium nitrate addition, aluminum sulfate addition, and oxygenation. In our view, the deliberate addition of nitrate to lakes and reservoirs poses several risks that must be carefully considered when evaluating strategies to control sediment phosphorus release.