BACKGROUND: This randomized controlled trial compares the effects of walnuts, fish and the combination of the two on cardiovascular risk factors among overweight or obese females who were losing their weight. METHODS: Ninety-nine overweight and obese women were randomized to 3 weight-reducing diets: fish (300 g/week), walnut (18 walnuts/per week) or fish + walnut (150 g fish and 9 walnuts /week) for 12 weeks. Anthropometric indices, systolic & diastolic blood pressure, fasting blood glucose, inflammatory markers, serum lipids and coagulating factors were measured. RESULTS: The reduction in systolic blood pressure (SBP) (-5.0 ± 0.3 mm Hg, P = 0.01), fasting blood glucose (FBG) (-12.4 ± 1.9 mg/ dL, P = 0.001), low-density lipoprotein (LDL) (-6.2 ± 1.3 mg/dL, P = 0.03), high-sensitivity C-reactive protein (CRP) (-0.51 ± 0.08 mg/L, P < 0.001), D-dimer (-0.45 ± 0.07 mg/dL, P < 0.001), fibrinogen (-22.4± 4.5 mg/dL, P < 0.001), alanine aminotransferase (ALT) (-6.4 ± 0.9 mg/dL, P < 0.001), aspartate aminotransferase (AST) (-6.3 ± 0.9 IU/L, P = 0.01), tumor necrosis factor-alpha (TNF-α) (-0.08 ± 0.02 ng/mL, P = 0.01), interleukin 6 (IL-6) (-1.6 ± 0.1 ng/mL, P < 0.001) and increase in high-density lipoprotein (HDL) (3.6 ± 0.2 mg/dL, P < 0.001) were significantly higher in the group randomized to the fish + walnut diet compared with either the fish group or the walnut group. A significant decrease was seen in TG (-7.3 ± 1.1 mg/dL, P < 0.001) and diastolic blood pressure (DBP) (-2.0 ± 0.06 mm Hg, P = 0.01) levels in the fish group and the walnut group compared with the fish + walnut group. The change in other risk factors was not different among groups. CONCLUSION: The present study shows that the combination of marine and plant omega-3 together is more effective on blood pressure levels, fasting blood glucose, inflammatory markers, serum lipids and coagulating factors than the fish or walnut in isolation.