The objective of this research is to determine the effect of depuration treatment on the reduction of heavy metals content (Hg and Pb) in green mussels (Perna viridis) culture in Jakarta Bay waters. This research used a block randomized design with 2 blocks (location), and 4 treatments: A0 (control), A1 (heated), A2 (flowing water), and A3 (EDTA) with 3 replications. The analysis of heavy metals content was performed with Atomic Absorption Spectroscopy (AAS) method, analysis data by ANOVA, Duncan and Dunnett test. The result of the experiment showed that the lowest heavy metal content is on the treatment A2 (flowing water). There is no significant difference (P > 0.05), between Cilincing and Kamal estuaries location. Effect of the depuration showed a significant result (P < 0.05) on heavy metal reduction. The Dunnet test showed that treatment of A1 and A2 are significantly different (P > 0.05) with control, but there are no significant difference (P < 0.05) between treatment of A3 (EDTA) with control. The average concentration of Hg and Pb in green mussels (Perna viridis) on the treatment A0 (control) are 0.09 ppm and 5.98 ppm, treatment A1 (heating) 0.045 ppm and 4.05 ppm, treatment A2 (flowing water) 0.035 ppm and 2.98 ppm, and treatment A3 (EDTA) 0.05 ppm and 5.31 ppm. Lead (Pb) content in green mussels (Perna viridis) have already above the threshold value, stated by the Ministry of Marine Affairs and Fishery regulation (Kepmen No.KEP.17/MEN/2004) about sanitation shells system for Indonesian fishery. From the result, it could be predicted that the accumulation of heavy metal load comes from many industries and domestic wastes in Jakarta Bay waters and surrounding, so it is not safe for consumption.