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In order to better understand the environmental risks of the rare earth elements (REEs), it is necessary to determine their fate and biological effects under environmentally relevant conditions (e.g. at low concentrations, REE mixtures). Here, the unicellular freshwater microalga, Chlamydomonas reinhardtii, was exposed for 2 h to one of three soluble REEs (Ce, Tm, Y) salts at 0.5 µM or to an equimolar mixture of these REEs. RNA sequencing revealed common biological effects among the REEs. Known functions of the differentially expressed genes support effects of REEs on protein processing in the endoplasmic reticulum, phosphate transport and the homeostasis of Fe and Ca. The only stress response detected was related to protein misfolding in the endoplasmic reticulum. When the REEs were applied as a mixture, antagonistic effects were overwhelmingly observed with transcriptomic results suggesting that the REEs were initially competing with each other for bio-uptake. Metal biouptake results were consistent with this interpretation. These results suggest that the approach of government agencies to regulate the REEs using biological effects data from single metal exposures may be a largely conservative approach.