The lampricide 3-trifluoromethyl-4-nitrophenol (TFM) has been used in liquid form to control larval sea lamprey (Petromyzon marinus) in Great Lakes tributaries since the late 1950s. In the 1980s a dissolvable TFM bar was developed as a supplemental tool for application to small tributaries as a deterrent to larvae seeking water not activated with TFM. The size, mass, and number of bars needed in some streams, as well as the location of the streams, limit the utility of a TFM bar. The development and use of an alternative niclosamide bar has the potential to use fewer bars to achieve similar results. However, the use of a niclosamide bar is dependent upon its larval deterrent capability compared to the TFM bar. In this study, we developed a laboratory-scale, simulated stream fluvarium with several avoidance areas including two side channels and a seep. The objective was to evaluate the deterrent capabilities of TFM and niclosamide. We found similar behavioral responses, with TFM and niclosamide having similar capabilities to prevent sea lamprey from seeking refuge in side channels and seep avoidance areas. TFM-treated side channels and seep increased sea lamprey occupancy in the main channel 2.56 times more than the untreated-controls (95% CI 1.63–4.14) whereas niclosamide-treated side channels and seep increased sea lamprey occupancy of the main channel 2.68 times more than the untreated-controls (95% CI 1.72–4.32). These responses indicate a niclosamide bar would effectively prevent sea lamprey escapement into freshwater during a lampricide treatment at concentrations unlikely to harm aquatic organisms.