Titanium dioxide nanoparticles (TiO₂ NPs) have attracted considerable concerns due to the increasing production and widespread applications, while their influences on other co-existing pollutants in real environment are not well studied. In this paper, the colloidal stability of TiO₂ NPs in the exposure medium was first evaluated, and then, the medium was modified so that TiO₂ NP suspension remained stable over the exposure period. Finally, using the optimized exposure medium, the effects of cadmium (Cd) and lead (Pb) on Daphnia magna both in the absence and presence of TiO₂ NPs were investigated. Results showed that 2 mg L⁻¹ of TiO₂ NPs was well dispersed in 1:20 diluted Elendt M7 medium without EDTA, and no immobility was observed. The presence of the nanoparticles increased the bioaccumulation and toxicity of Cd to the daphnias. On the contrary, while Pb bioaccumulation was enhanced by three to four times, toxicity of Pb was reduced in the presence of TiO₂ NPs. The decreased toxicity of Pb was more likely attributed to the decreased bioavailability of free Pb ion due to adsorption and speciation change of Pb in the presence of TiO₂ NPs. Additionally, surface-attached TiO₂ NPs combined with adsorbed heavy metals caused adverse effects on daphnia swimming and molting behavior, which is supposed to lead to chronic toxicity.