Low dissolved oxygen concentrations, caused by density stratification of the water column and excess nutrient inputs, occur in many aquatic habitats. Laboratory experiments we conducted indicated that low dissolved oxygen has the potential to strongly alter the absolute and relative importance of a suite of estuarine predators of fish larvae. At dissolved oxygen concentrations ≤ 2 mg 1−1, predation on naked goby Gobiosoma bosc larvae by an important invertebrate predator of plankton in Chesapeake Bay (the sea nettle scyphomedusa Chrysaora quinquecirrha) increased. In contrast, at the same oxygen concentrations, predation by 2 vertebrate predators, juvenile striped bass Morone saxatilis and adult naked goby, decreased. Changes in consumption of larvae most likely resulted from impaired ability of larvae to escape the scyphomedusa, and decreased attack rates by adult and juvenile fishes. Fish predators increased gill ventilation rates even at oxygen levels higher than those leading to decreased predation. However, we could detect no comparable change in behavior of the sea nettle even at 1 mg 1−1, the lowest oxygen concentration tested. The observed changes in trophic interactions occurred at dissolved oxygen concentrations that are not lethal during short exposures, and that commonly occur in the Chesapeake Bay and other eutrophic estuaries during summer. Thus, low oxygen has the potential to cause significant changes in the importance of alternate trophic pathways in estuarine systems.