- Contaminants are ubiquitous in the environment, often reaching aquatic systems. Combinations of forestry use pesticides have been detected in both water and aquatic organism tissue samples in coastal systems. Yet, most toxicological studies focus on the effects of these pesticides individually, at high doses, and over acute time periods, which, while key for establishing toxicity and safe limits, are rarely environmentally realistic. We examined chronic (90 days) exposure by the soft-shell clam, Mya arenaria, to environmentally relevant concentrations of four pesticides registered for use in forestry (atrazine, 5 μg/L; hexazinone, 0.3 μg/L; indaziflam, 5 μg/L; and bifenthrin, 1.5 μg/g organic carbon (OC)). Pesticides were tested individually and in combination, except bifenthrin, which was tested only in combination with the other three. We measured shell growth and condition index every 30 days, as well as feeding rates, mortality, and chemical concentrations in tissue from a subset of clams at the end of the experiment to measure contaminant uptake. Indaziflam caused a high mortality rate (max. 36%), followed by atrazine (max. 27%), both individually as well as in combination with other pesticides. Additionally, indaziflam concentrations in tissue (61.70–152.56 ng/g) were higher than those of atrazine (26.48–48.56 ng/g), despite equal dosing concentrations, indicating higher tissue accumulation. Furthermore, clams exposed to indaziflam and hexazinone experienced reduced condition index and clearance rates individually and in combination with other compounds; however, the two combined did not result in significant mortality. These two compounds, even at environmentally relevant concentrations, affected a non-target organism and, in the case of the herbicide indaziflam, accumulated in clam tissue and appeared more toxic than other tested pesticides. These findings underscore the need for more comprehensive studies combining multiple compounds at relevant concentrations to understand their impacts on aquatic ecosystems.