The introduction of predatory Nile perch (Lates niloticus) into the Lake Victoria basin coincided with a dramatic decline in fish diversity. However, remnant populations of indigenous fishes persist in lagoons and satellite lakes separated from the main lakes by extensive areas of swamp, while other indigenous species find refuge in ecotonal areas at edges of marginal swamps in the main lakes. Low-oxygen conditions in these wetlands may physiologically stress Nile perch and therefore minimize its interaction with prey species. This study examined the low-oxygen tolerance of Nile perch collected from Lake Nabugabo, Uganda, by documenting behavioural and physiological strategies that relate to oxygen uptake. In response to hypoxia, Nile perch used aquatic surface respiration (ASR) at the air-water interface, ventilating their gills with water from the surface. However, several lines of evidence suggest that Nile perch in Lake Nabugabo are inefficient at ASR and relatively intolerant of low oxygen conditions. These include high thresholds for ASR relative to other indigenous fishes of the Lake Victoria basin, no decrease in gill ventilation rate with the onset of ASR, a faster time to loss of equilibrium in hypoxic conditions than other species from the region, and a high critical oxygen tension (24 mm Hg).