BACKGROUND: Recent studies indicated that dietary n-3 polyunsaturated fatty acids (PUFAs) increase circulating adiponectin concentrations in rodents. OBJECTIVE: We aimed to investigate whether a diet rich in n-3 PUFAs increased plasma concentrations of total or high-molecular-weight (HMW) adiponectin in healthy overweight-to-moderately obese men and women. DESIGN: Sixteen women and 10 men with a body mass index (in kg/m(2)) between 28 and 33 were randomly assigned to consume a diet rich in n-3 PUFAs (3.5% of energy intake) from both plant and marine sources or a control diet (0.5% of energy intake from n-3 PUFAs). For the first 2 wk, these diets were consumed under isocaloric conditions; then followed a 12-wk period of ad libitum consumption that was associated with a moderate loss of approximately 3.5% of body weight in both groups. Total and HMW adiponectin plasma concentrations were measured before and after each diet phase. RESULTS: Plasma fasting adiponectin concentrations did not change during the isocaloric period, but they increased modestly ( approximately 10%) during the ad libitum period when subjects lost weight [P = 0.009 for time in repeated-measures analysis of variance] and to a similar extent in subjects consuming the control (x +/- SD: 0.42 +/- 0.69 microg/mL) and n-3 PUFA (0.45 +/- 0.85 microg/mL) diets (P = 0.920 for time x treatment interaction). Plasma concentrations of HMW adiponectin did not change significantly during the study. CONCLUSION: Dietary n-3 PUFAs consumed at levels of 3.5% of energy intake do not significantly increase plasma or HMW adiponectin concentrations in overweight-to-moderately obese healthy men and women over the course of 14 wk.