Antarctic krill, also known as Euphausia superba, is a marine crustacean rich in both eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). We tested the hypothesis that krill oil would increase plasma concentrations of EPA and DHA without adversely affecting indicators of safety, tolerability, or selected metabolic parameters. In this randomized, double-blind parallel arm trial, overweight and obese men and women (N = 76) were randomly assigned to receive double-blind capsules containing 2 g/d of krill oil, menhaden oil, or control (olive) oil for 4 weeks. Results showed that plasma EPA and DHA concentrations increased significantly more (P < .001) in the krill oil (178.4 +/- 38.7 and 90.2 +/- 40.3 micromol/L, respectively) and menhaden oil (131.8 +/- 28.0 and 149.9 +/- 30.4 micromol/L, respectively) groups than in the control group (2.9 +/- 13.8 and -1.1 +/- 32.4 micromol/L, respectively). Systolic blood pressure declined significantly more (P < .05) in the menhaden oil (-2.2 +/- 2.0 mm Hg) group than in the control group (3.3 +/- 1.5 mm Hg), and the response in the krill oil group (-0.8 +/- 1.4 mm Hg) did not differ from the other 2 treatments. Blood urea nitrogen declined in the krill oil group as compared with the menhaden oil group (P < .006). No significant differences for other safety variables were noted, including adverse events. In conclusion, 4 weeks of krill oil supplementation increased plasma EPA and DHA and was well tolerated, with no indication of adverse effects on safety parameters.