The effect of copper-imposed oxidative stress on isocitrate lyase (ICL) activity was studied in a Chlamydomonas reinhardtii wild type and a copper-tolerant pleiotropic mutant strain. Suspension batch bioassays were performed adding copper chloride under moderate irradiation. Two harvest points were selected to represent the acute and restoration phases and oxidative stress indicators were measured: antioxidative metabolites, phenolic compounds, ascorbic acid, abundance of thiobarbituric reactive substances, and activities of detoxifying enzymes such as catalase and ascorbate peroxidase. Copper stress under moderate irradiance favours acetate assimilation through enhanced ICL activity, especially in the acute phase. Though the mutant strain exhibited at least twofold ICL activity in the acute phase compared to the wild type, there was no significant difference in copper tolerance between strains. The higher ICL activity under copper stress may be an adaptation to promote mixotrophic organic carbon assimilation when photosynthetic carbon dioxide fixation is impaired. Thus, the higher ICL activity has the potential to be a useful indicator in acetate-flagellate bioassays.