Indo-Pacific lionfish (Pterois spp.) have become established throughout the Caribbean and the coastal regions of the Gulf of Mexico and western Atlantic Ocean from North Carolina to central Brazil. Lionfish may also invade estuaries, as they tolerate salinities down to 4‰. We hypothesize that the functional characteristics of their visual system (which evolved in the clear tropical waters of the Indo-Pacific) or their inability to tolerate hypoxia will limit the capacity of lionfish to occupy these areas. We assessed the former with corneal electroretinography and the latter with intermittent-flow respirometry. The luminous sensitivity, temporal resolution (quantified as flicker fusion frequency), and spectral sensitivity of the lionfish visual system are like those of native piscivores, indicating that their visual system will be functional under estuarine photic conditions and allow lionfish to be effective piscivores. In contrast, acute exposure to reduced oxygen levels (equivalent to those commonly occurring in mid-Atlantic and Gulf of Mexico estuaries) exceeded the physiological tolerances of lionfish. We therefore conclude that hypoxia will control or limit estuarine invasion.