The lampricides 3-trifluoromethyl-4-nitrophenol (TFM) and 2′, 5-dichloro-4′-nitrosalicylanilide (niclosamide) are used to control sea lamprey (Petromyzon marinus), an invasive species in the Great Lakes. Age-0 lake sturgeon (Acipenser fulvescens), a species of conservationconcern, share similar stream habitats with larval sea lampreys and these streams can be targeted for lampricide applications on a 3- to 5-year cycle. Previous laboratory researchfound that lake sturgeon smaller than 100 mm could be susceptible to lampricide treatments. We conducted stream-side toxicity (bioassay) and in situ studies in conjunction with 10 lampricide applications in nine Great Lakes tributaries to determine whether sea lamprey treatments could result in in situ age-0 lake sturgeon mortality, and developed a logistic model to help predict lake sturgeon survival during future treatments. In the bioassays the observed concentrations where no lake sturgeon mortality occurred (no observable effect concentration, NOEC) were at or greater than the observed sea lamprey minimum lethal concentration (MLC or LC99) in 7 of 10 tests. We found that the mean in situ survival of age-0 lake sturgeon during 10 lampricide applications was 80%, with a range of 45–100% survival within streams. Modeling indicated that in age-0 lake sturgeon survival was negatively correlated with absolute TFM concentration and stream alkalinity, and positively correlated with stream pH and temperature. Overall survival was higher than expected based on previous research, and we expect that these data will help managers with decisions on the trade-offs between sea lamprey control and the effect on stream-specific populations of age-0 lake sturgeon.