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This work demonstrated a 10-day batch culture experiment to test the physiology and toxicity of harmful dinoflagellate Karenia mikimotoi in response to ocean acidification (OA) under two different phosphate concentrations. Cells were previously acclimated in OA (pH = 7.8 and CO2 = 1100 mu atm) condition for about three months before testing the responses of K. mikimotoi cells to a two-factorial combinations experimentation. This work measured the variation in physiological parameters (growth, rETR) and toxicity (hemolytic activity and its toxicity to zebrafish embryos) in four treatments, representing two factorial combinations of CO2 (450 and 1100 mu atm) and phosphate concentration (37.75 and 4.67 umol l(-1)). Results: OA stimulated the faster growth, and the highest rETR(max) in high phosphate (HP) treatment, low phosphate (LP) and a combination of high CO2 and low phosphate (HC*LP) inhibited the growth and E-k in comparison to low COs*high phosphate (LCHP) treatment. The embryotoxicity of K. mikimotoi cells enhanced in all high CO2 (HC) conditions irrespective of phosphate concentration, but the EC50 of hemolytic activity increased in all high CO2 (HC) and low phosphate (LP) treatments in comparison of LCHP. Ocean acidification (high CO2 and lower pH) was probably the main factor that affected the rETR(max), hemolytic activity and embryotoxicity, but low phosphate was the main factor that affected the growth, alpha, and E-k. There were significant interactive effects of OA and low phosphate (LP) on growth, rETR(max), and hemolytic activity, but there were no significant effects on alpha, E-k, and embryotoxicity. If these results are extrapolated to the aquatic environment, it can be hypothesized that the K. mikimotoi cells were impacted significantly by future changing ocean (e.g., ocean acidification and nutrient stoichiometry).