Synthetic musks, such as 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8, -hexamethyl-cyclopenta[g]benzopyran (HHCB), are organic compounds found in several personal care products. HHCB (present in the formulation of galaxolide) is one of the most frequently used synthetic musk compounds globally and is commonly detected in aquatic waterways, leading to its classification as an “emerging contaminant.” Previous studies have mostly evaluated the toxicity of HHCB using water-only testing. However, its high Log Kow (5.9) indicates the compound will partition to sediments preferentially. Three benthic invertebrates, Chironomus dilutus, Hyalella azteca, and Lumbriculus variegatus, were exposed to HHCB-spiked sediment using both acute (10-d) and chronic (28-d) bioassays. Additionally, growth was evaluated by measuring weight (for L. variegatus) and length (for H. azteca and C. dilutus) of surviving organisms in chronic bioassays to evaluate sublethal effects. The acute and chronic LC50s for HHCB ranged from 229 – 741 mg/kg (2313 – 7484 µg/g OC) for all three species, which is above concentrations commonly detected in aquatic waterways. Additionally, effects on growth (i.e., weight and length) were noted in two of the three organisms in the chronic bioassays (with C. dilutus being the exception), but only at concentrations higher than environmentally relevant. Molecular-level evaluations of L. variegatus and C. dilutus exposed to concentration near the LC50 value were conducted. In C. dilutus, markers of oxidative stress (glutathione-s-transferase) and endocrine disruption (estrogen-related receptor) were both significantly decreased in the treatment group compared to controls by 0.7-fold and 1.9-fold, respectively. However, at more environmentally relevant concentrations of HHCB, these effects were not significant for all three benthic organisms. Regardless, the noted changes in endocrine-related genes suggest that future studies are warranted to understand long-term, low-level effects. More sensitive endocrine-based endpoints, such as emergence (for C. dilutus) and molting (for H. azteca), are needed to examine the risk of this emerging contaminant at environmentally relevant concentrations.