The cross-flow ultrafiltration and radiotracer techniques were used to study the influences of natural dissolved organic carbon (DOC) and colloidal organic carbon (COC) on the bioavailability of Ag, Cd, and Cr to the green mussel Perna viridis. We examined the uptake of these metals by the mussels at different concentrations of DOC and COC from different origins (estuarine, coastal, and diatom decomposed). Using the DOC originating from the decomposed diatom ( Thalassiosira pseudonana), we demonstrated that Cd and Cr uptake, quantified by the concentration factor (DCF), increased linearly with increasing DOC concentration. There was, however, no consistent influence of natural DOC concentration on the metal uptake when the DOC was obtained from different sources of seawater (coastal and estuarine). The influences of COC on metal bioavailability were metal-specific and dependent on the geochemical properties of colloids and colloid–metal complexation. Cd uptake rate was not influenced by the COC concentrations. Uptake of diatom-decomposed colloidal Cr was enhanced by 3.4×, whereas the uptake of diatom-decomposed colloidal Ag was decreased by 8.2× compared with the uptake of low molecular weight Cr and Ag (<1 kDa). The uptake of diatom-decomposed colloidal Cr and Ag was generally lower than the uptake of metals bound with the same type of colloids for 2 days. Further aging of the colloid-metal binding reduced metal bioavailability to the mussels. In the presence of different sizes of colloidal particles where there was no major binding of colloids with the metals, metal uptake by the mussels was not influenced by different COC concentrations. Overall, our study suggests that although metal dissociation from colloids may be an important step for the uptake of colloidal metals, other mechanisms such as pinocytosis and co-transport may also be involved in the uptake of these metals, especially in aquatic environments with high DOC and COC concentrations.