Freshwater mussels are in decline worldwide, but it remains challenging to link specific stressors to mussel declines. The clubshell mussel (Pleurobema clava) is a federally endangered species that spends most of its life completely buried beneath stream sediments. We tested the hypothesis that clubshell’s decline stems, in part, from low pore water dissolved oxygen (DO) concentrations and toxic ammonia (NH3) levels, resulting from sedimentation of interstitial pore spaces. We measured pore water DO, NH3, interstitial sedimentation rates, and sediment organic matter content in the Tippecanoe River (Indiana, USA) at sites that spanned a range of clubshell populations, including two sites devoid of clubshell. We found little evidence for pore water NH3 stress, but pore water DO generally declined with clubshell population and dipped below stress thresholds more frequently at non-clubshell sites than at sites with clubshell. In addition, interstitial sedimentation rates generally increased as clubshell populations declined, suggesting that the low DO concentrations were the result of decreased pore water – surface water exchange. As a result, we conclude that maintaining or improving habitat for clubshell mussels will require the reduction of riverine sediment loading.