There is emerging evidence that persistent organic pollutants (POPs) can increase the risk of various chronic diseases. As POPs mainly bioaccumulate in adipose tissue, weight change can affect serum concentrations of POPs. However, there are few population-based studies on effects of long-term weight change on serum concentrations of POPs. We examined associations between self-reported weight change over 1 year and 10 years and serum concentrations of seven POPs in 1099 adults aged ≥ 40. Serum concentrations of most POPs were higher in those with long-term weight loss, whereas they were lower in those with long-term weight gain. Adjusted correlation coefficients of each POP with weight change for 10 years were -0.23 (P < 0.01) for trans-nonachlor, -0.16 (P < 0.01) for p,p'-dichlorodiphenyldichloroethylene, and -0.21 (P < 0.01) for β-hexachlorocyclohexane, -0.16 (P < 0.01) for PCB169, -0.20 (P < 0.01) for PCB180 and -0.17 (P < 0.01) for 1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin. Weight change for 1 year showed similar but weaker associations, compared with those of long-term weight changes. Although both beneficial health effects after weight loss and harmful health effects after weight gain are generally expected, changes in serum concentrations of POPs in relation to weight change may act on health in directions opposite to what we expect with weight change.