The influence of dissolved organic carbon (DOC), in the form of Suwannee River fulvic acid (SRFA), on uranium (U) toxicity to the unicellular eukaryote, Euglena gracilis (Z strain), was investigated at pH 6. In a background medium without SRFA, exposure of E. gracilis to 57 μg L−1 U resulted in a 50% reduction in growth (IC50). The addition of 20 mg L−1 DOC (as SRFA), reduced U toxicity 4 to 5-fold (IC50 increased to 254 μg L−1 U). This reduction in toxicity was also evident at more sensitive effect levels with a 10% reduction in growth (IC10) occurring at 5 μg L−1 U in the background medium and at 17 μg L−1 U in the SRFA medium, respectively. This amelioration of toxicity with the addition of SRFA was linked to a decrease in the bioavailability of U, with geochemical speciation modelling predicting 84% of U would be complexed by SRFA. The decrease in bioavailability of U in the presence of SRFA was also evident from the 11–14 fold reduction in the cellular concentration of U compared to that of E. gracilis in the background medium. Stepwise multiple linear regression analyses indicated that UO22+ alone explained 51% of the variation in measured U toxicity to E. gracilis. Preliminary U exposures to E. gracilis in the presence of a reactive oxygen species probe, suggest exposure to ≥60 μg L−1 U may induce oxidative stress, but this endpoint was not considered to be a sensitive biological indicator.