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Aims: The objective of this study was to determine the effects of intake of polyphenols from Ecklonia cava on spatial task performance and nervous fatty acid composition in mice fed with a high-fat diet. Methods: Thirty mice were randomly divided into three groups; each group consisted of ten mice. The control group was fed 5% soybean oil as a fat source, whereas the high fat (HF) group was fed a 15% lard diet and the polyphenol (ECP) group was maintained on the HF diet plus 1% E. cava polyphenols. Results: The ECP group exhibited a short escape latency and better memory retention in the Morris water maze test compared with the control and HF groups (P<0.05). In addition, the ECP group showed a greater increase in avoidance latency than that of the HF group (P<0.05). Moreover, the consumption of polyphenols from E. cava presented higher levels of DHA in the brain and retina (P<0.05). Conclusion: This study suggested the positive effects of polyphenols from E. cava on memory retention, which might be partially attributed to the increased levels of DHA in the brain.