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Due to the increase in the use of phytosanitary products during the last few decades, the importance to study the effect of pesticide mixtures has been established. In this study, we investigated the acute toxicity of two model insecticides, chlordecone (CLD) and pyriproxyfen (PXF), alone and in mixtures, in the estuarine copepod Eurytemora affinis. After 48 h of exposure, the relative LC50 were 73.24 and 131.61 μg/L for PXF and CLD, respectively. The lower concentration tested (10 μg/L) did not affect the mortality of E. affinis whatever the considered chemical compound. To understand the interaction between compounds in mixture, the results were fitted to the concentration addition, Vølund, and Hewlett models. The best fit was obtained with the Hewlett model, suggesting a synergistic effect of the mixture.