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Abstract Saprolegnia parasiticais an oomycete pathogen responsible for saprolegniasis diseases that result in large production losses in the catfish and salmon aquaculture industry. The use of copper sulfate as an anti-Saprolegnia treatment has been reported as an alternative to malachite green, formaldehyde and hydrogen peroxide treatment methods. The current study investigates a new strategy to inhibitSaprolegnia parasiticagrowth by combining copper and ionophores at low levels. The chemical agents tetraethylthiuram disulfide (TDD), ciclopirox olamine (CLP), 2-mercaptopyridine N-oxide (MPO), 5-chloro-8-hydroxy-7-iodoquinoline (CHI), 5,7-dichloro-8-hydroxyquinoline (DHQ) and 8-Quinolinol (8QN) were identified to inhibitS. parasiticagrowth in a copper-dependent manner. At concentrations below the lethal dose of individual ionophore, increasing copper concentrations resulted in synergeticS. parasiticagrowth inhibition. The addition of the exogenous copper chelator bathocuproine sulfate (BCS), reversed the inhibition ofS. parasiticagrowth by TDD, CLP, MPO, and 8QN but not CHI and DHQ. Our data demonstrates that ionophores, in combination with low levels of copper, can effectively limitS. parasiticagrowth both in a liquid and solid support growth environment. Investigations into the underlying mechanism of Cu-ionophore toxicity are discussed.