Biomarkers of oxidative stress metabolism and the innate immune response were examined in gill and head kidney tissue of wild-caught yellow perch (Perca flavescens) collected from four sites ranging in type and degree of metal pollution in the St. Lawrence River, Quebec, Canada. Sites were ranked as follows: Ile Dorval<Iles aux Sables<Ilet Vert<Beauharnois. Biomarker measurements did not correspond completely to the perceived pollution gradient. Total protein content was highest at a site 4 km downstream of municipal effluents (Ilet Vert) exposed to moderate and high levels of heavy metals and faecal coliforms, respectively. Thiol content was highest at the reference site (Ile Dorval) with the lowest contaminant levels. Glutathione-S-transferase (GST) activity was highest in fish from the site furthest downstream that was exposed to moderate metal contamination (Iles aux Sables). Glutathione reductase (GRd) activity was high in both gill and head kidney tissue of fish from the reference site (Ile Dorval) and highest in the kidney of fish from the most contaminated site (Beauharnois). Catalase activity was highest in head kidney tissue in fish from this latter site. Ceruloplasmin activity was lowest in head kidney from fish collected at the reference site and highest at Beauharnois. Lysozyme activity was lowest in head kidney tissue from fish at the reference site and highest in tissue from fish at Ilet Vert, downstream of municipal effluents. These results suggest that the direction and magnitude of oxidative stress biomarker response and innate immune function biomarker response vary between tissues and among complex mixtures of contaminants, complicating interpretation of results. Results further suggest that bacterial loading, as measured by faecal coliforms, affects the oxidative stress metabolism and the innate immune response.