Uranium (U) mining and milling release arsenic (As), nickel (Ni) and U to receiving waters, which accumulate in sediments. The objective of the present study was to investigate if As, Ni, and U concentrations in tissue residue of Hyalella azteca, overlying water, sediment porewater, and solids could predict juvenile and adult survival and growth in conditions similar to lake sediments downstream of U mines and mills. We conducted 14-d static sediment toxicity tests spiked with U, As, and Ni salts. For U, we spiked uranyl nitrate with sodium bicarbonate to limit U precipitation once in contact with circumneutral sediment. The median lethal concentrations for As, Ni, and U of juveniles and adults based on measured concentrations in sediments were 134 and 165 mg/g, 370 and 787 mg/g, and 48 and 214 mg/g, respectively. Adult survival and growth linearly decreased with increasing bioaccumulation. For juveniles, metal accumulation linearly predicted survival. We calculated median lethal body concentrations for juveniles and adults of 5 and 36 mg As/g, 14 and 49 mg Ni/g, and 0.4 and 1.0 mg U/g. The concentrations of As, Ni, and U in tissue residue leading to a 20% decrease in adult growth were 32 mg As/g, 44 mg Ni/g, and 1 mg U/g. Overall, the present study showed that U was the most toxic element, followed by As and Ni; that juveniles were more sensitive to the 3 metals tested than adults; and that threshold body concentrations can support assessment of benthic invertebrate community impairment.