The Matāura River is the sixth largest river system in New Zealand and has long been subject to agricultural, industrial, and residential land use activities. The catchment has geographic and economic value and is of great cultural importance for local Māori, who have concerns over potential adverse impacts that anthropogenic stressors exert on the health of the river. There is a dearth of information on the impacts of these stressors towards the health of native species such as the longfin eel Anguilla dieffenbachii. This study assessed the environmental status of the Matāura River using biological and chemical methodologies incorporating A. dieffenbachii as a bioindicator species for exposure to combined anthroprogenic stressors. A range of biomarker endpoints were measured in caged and wild-caught eels (when available) to characterize site-specific responses to combined anthropogenic stressors. While there was no clear indication of cumulative impacts moving from pristine headwaters to the lower reaches of the Matāura River biomarkers of xenobiotic metabolization were induced in A. dieffenbachia and there was evidence of chemical contamination in sediments and tissues.