Understanding how key-species respond to anthropogenic stress such as chemical pollution is critical for predicting ecosystem changes. Little is however known about the intra-specific variability in the physiological and biochemical traits involved in contaminant exposure responses. Here, we explored this idea by exposing the Baltic amphipod Monoporeia affinis from two sites, one moderately polluted and one more pristine, to a sediment spiked with PAHs and PCBs. We evaluated the amphipods responses related to feeding, growth, a stress biomarker (acetylcholinesterase [AChE] inhibition) and stable isotope (delta C-13 and delta N-15) composition including isotope niche analyses. More adverse responses were expected in animals from the low-pollution site than those from the high-pollution site due to tolerance development in the latter. Amphipods from both populations showed a similar to 30% AChE inhibition when exposed to the contaminant spiked sediment. However, both controls and exposed amphipods from the high-pollution site had higher survival, nutrient uptake and condition status than the amphipods from the low-pollution site, which did not feed on the added diatoms as indicated by their isotope values. We found no signs of population-specific responses in physiological adjustments to contaminants with regard to classic ecotoxicological biomarkers such as AChE inhibition and growth status. Instead, isotope niche analyses proved useful in assessing contaminant stress responses at the population level.