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Changing salinity in estuaries due to sea level rise and altered rainfall patterns, as a result of climate change, has the potential to influence the interactions of aquatic pollutants as well as to alter their toxicity. From a chemical property point of view, ionic concentration can increase the octanol–water partition coefficient and thus decrease the water solubility of a compound. Biologically, organism physiology and enzyme metabolism are also altered at different salinities with implications for drug metabolism and toxic effects. This highlights the need to understand the influence of salinity on pesticide toxicity when assessing risk to estuarine and marine fishes, particularly considering that climate change is predicted to alter salinity regimes globally and many risk assessments and regulatory decisions are made using freshwater studies. Therefore, we exposed the Inland Silverside (Menidia beryllina) at an early life stage to seven commonly used pesticides at two salinities relevant to estuarine waters (5 PSU and 15 PSU). Triadimefon was the only compound to show a statistically significant increase in toxicity at the 15 PSU LC50. However, all compounds showed a decrease in LC50 values at the higher salinity, and all but one showed a decrease in the LC10 value. Many organisms rely on estuaries as nurseries and increased toxicity at higher salinities may mean that organisms in critical life stages of development are at risk of experiencing adverse, toxic effects. The differences in toxicity demonstrated here have important implications for organisms living within estuarine and marine ecosystems in the Anthropocene as climate change alters estuarine salinity regimes globally.