The elderly are known to have an inadequate immune response to influenza vaccine. Mekabu fucoidan (MF), a sulfated polysaccharide extracted from seaweed, was previously shown to have an immunomodulatory effect. We therefore investigated antibody production after influenza vaccination in elderly Japanese men and women with and without oral MF intake. A randomized, placebo-controlled, double-blind study was conducted with 70 volunteers >60 y of age. They were randomly assigned to 1 of 2 groups, consuming either MF (300 mg/d) or placebo for 4 wk, and then given a trivalent seasonal influenza vaccine. Serum was sampled at 5 and 20 wk after vaccination to measure the hemagglutination inhibition titer and natural killer cell activity. The MF group had higher antibody titers against all 3 strains contained in the seasonal influenza virus vaccine than the placebo group. Titers against the B/Brisbane/60/2008 (B) strain increased substantially more in the MF group than in the placebo group over the product consumption period. The immune response against B antigen met the European Union Licensure criteria regarding the geometric mean titer ratio in the MF group (2.4), but not in the placebo group (1.7). In the MF group, natural killer cell activity tended to increase from baseline 9 wk after MF intake (P = 0.08). However, in the placebo group no substantial increase was noted at 9 wk, and the activity decreased substantially from 9 to 24 wk. In the immunocompromised elderly, MF intake increased antibody production after vaccination, possibly preventing influenza epidemics.