For the prediction of metals mixture ecotoxicity, the BLM approach is promising since it evaluates the amount of metals accumulated on the biotic ligand on the basis of water chemistry, i.e. species (major cations) competing with metals, and related toxicity. Based on previous work by Farley et al. 2015 (MMME research project), this study aimed at modelling toxicity of Cd:Cu mixtures (0:1–1:1–1:0–1:2 − 1:3 − 2:1–3:1–4:1–5:1–6:1) to the crustacean Daphnia magna (48h immobilization tests) and the microalga Pseudokirchneriella subcapitata (72h growth inhibition tests). The USGS model was chosen, assuming additivity of effects and accumulation of metals on a single site. The assumption that EDTA could contribute to toxicity through metals complexing was also tested, and potential effects due to reduction of ions Ca2+ absorption by metals were considered. Modelling started with parameter values of Farley et al. 2015 and some of these parameters were adjusted to fit modelled data on observed data. The results show that toxicity can be correctly predicted for the microalgae and that the hypothesis of additivity is verified. For daphnids, the prediction was roughly correct, but taking into account CuEDTA led to more realistic parameter values close to that reported by Farley et al. 2015. However, It seems that, for daphnids responses, metals interact either antagonistically or synergistically depending on the Cu:Cd ratio. Furthermore, synergy could not be explained by additional effects linked to a reduction of Ca absorption since this reduction, mainly due to Cd, increased inversely to synergy. Finally, the USGS model applied to our data was able to predict Cu:Cd mixture toxicity to microalgae and daphnids, giving rise to estimated EC50s roughly reflecting EC50s calculated from observed toxicity.