Previous studies have reported high serum concentrations of polybrominated diphenyl ethers in residents of an electronic waste (e-waste) dismantling site in Guiyu town, South China. In this study, serum levels of Dechlorane Plus (DP), a chlorinated flame retardant of growing concern, were measured in residents of this region, and compared to those of a matched cohort from a nearby region in Haojiang, where fishing is the dominant industry. DP was detected in all the serum samples, with concentrations ranging from 7.8 to 465 ng/g lipid (median: 42.6 ng/g) and 0.93 to 50.5 ng/g lipid (median: 13.7 ng/g) in Guiyu and Haojiang, respectively. The Pearson's correlation coefficient between DP and decabromodiphenyl ether showed a positive relationship in Guiyu (r = 0.931, p < 0.01), but no correlation in Haojiang (r = 0.321, p = 0.34). The average anti-DP fractional abundances (f(anti) ratio) were 0.58 +/- 0.11 and 0.64 +/- 0.05 for Guiyu and Haojiang, respectively (p < 0.01). Tentatively identified dechlorination product ([-Cl + H]) was found in 19/40 serum samples (11/20 for Guiyu, 8/20 for Haojiang). These results suggest that the Guiyu and Haojiang cohorts experienced different dominant exposure routes. It is also possible that DP could bioaccumulate in a stereoselective manner, and undergo dechlorination metabolism. To the best of our knowledge, this is the first study to report DP levels in human serum. Further studies are needed to confirm the results of this study.