Little attention has been paid to the role of essential trace elements on the toxicity of another element. In this work, we examined if low concentrations of essential elements (Co, Mn, Zn, and Fe) modified the response of a freshwater green alga ( Chlamydomonas reinhardtii) to copper. To do so, we followed cell growth over 72 h in exposure media where the essential element concentrations were manipulated. Among these elements, iron proved to have a strong impact on the cells' response to copper. The free Cu2+ concentrations required to inhibit cellular growth by 50% (EC50) over 72 h decreased from 2 nM in regular Fe medium (10-17.6 M Fe3+) to 4 pM in low iron medium (10-19.0 M Fe3+); a 500-fold increase in toxicity. Moreover, at low Cu2+ concentrations (10-13.0 to 10-10.5 M), Cu uptake increased under low iron conditions but remain relatively stable under regular iron conditions. These results show clearly that iron plays a protective role against copper uptake and toxicity to C. reinhardtii. In freshwaters, iron is always abundant but the expected free iron concentrations in surface waters can vary between 10-14.0 to 10-20.0 M, depending on pH (e.g., when pH increases from 6 to 8). We conclude that copper toxicity in natural waters can be modulated by iron and that, in some conditions, the Biotic Ligand Model may need to be further developed to account for the influence of iron.