To investigate the effect of eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) supplementation on quality of life (QOL). Randomized, double-blind, placebo-controlled trial. Independently living individuals from the general older Dutch population. Three hundred two individuals aged 65 and older without depression or dementia. 1,800 mg/d EPA-DHA (n=96), 400 mg/d EPA-DHA (n=100), or placebo capsules (n=106) for 26 weeks. QOL was assessed using the short version of the World Health Organization QOL questionnaire (WHOQOL-BREF). The WHOQOL-BREF covers four domains: physical health, psychological health, social relationships, and satisfaction with environment. The total score range is 26 to 130, with higher scores indicating a more favorable condition. Mean age of the participants was 70, and 55% were male. Plasma concentrations of EPA-DHA increased 238% in the high-dose and 51% in the low-dose EPA-DHA group, reflecting excellent adherence. Median baseline total WHOQOL scores ranged from 107 to 110 in the three groups and were not significantly different from each other. After 26 weeks, the mean difference from placebo was -1.42 (95% confidence interval (CI)=-3.40-0.57) for the high-dose and 0.02 (95% CI=-1.95-1.99) for the low-dose fish oil group. Treatment with 1,800 mg or 400 mg EPA-DHA did not affect total QOL or any of the separate domains after 13 or 26 weeks of intervention. Supplementation with high or low doses of fish oil for 26 weeks did not influence the QOL of healthy older individuals.