Pest management strategies to reduce sea lice infestations in the salmon aquaculture industry include in-feed treatments with ivermectin (IVM) and SLICE® (active ingredient [AI] emamectin benzoate [EMB]), which can result in local contamination of the environment. These compounds partition to sediments, have moderate persistence, and may pose a risk to non-target benthic organisms. The sub-lethal effects of EMB, IVM and a combination of both (EMB/IVM) on the benthic amphipod Eohaustorius estuarius and polychaete Nereis virens at environmentally relevant sediment concentrations were examined in subchronic exposures (28-30-d). E. estuarius avoided sediment containing >50 μg/kg IVM alone and in combination with EMB. N. virens avoided sediment with >50 μg/kg IVM and >0.5 μg/kg EMB/IVM and exhibited impaired burrowing and locomotory behaviour with both treatments. Oxygen consumption was significantly decreased in E. estuarius (up to 50% compared to controls) and increased in N. virens (by ∼ 200%) when exposed to EMB, IVM and EMB/IVM at concentrations <5 μg/kg. IVM, SLICE® and combination exposures at environmentally relevant concentrations caused adverse effects in E. estuarius and N. virens which could significantly alter organism fitness near salmon aquaculture operations.