Acrylamide (ACR), organic compound, has been widely used owing to its broad spectrum of chemical and industrial applications. This study aims at evaluating the response of the antioxidant defense system, fatty acid composition and histopathological aspect in the respiratory trees of Holothuria forskali against ACR exposure under laboratory conditions. Holothuries were exposed to 5, 10, and 20 mg L À1 ACR concentrations for 5 days. A significant increase in n-6 polyunsaturated fatty acids levels especially the arachidonic acid (ARA, C20:4n-6) and its precursor linoleic acid (LA, C18:2n-6) in ACR-treated organisms. Regarding the n-3 levels, eicosapentaenoic acid (EPA, C20:5n-3) levels were increased in treated groups despite an acute decrease in docosahexaenoic acid (DHA, C22:6n-3) levels was observed. Our results showed a significant increase in hydrogen peroxide, malondialdehyde, protein carbonyl, and metallothionein levels along with an alteration of the antioxidants status in all treated sea cucumbers. The exposure to ACR prompted the inhibition of Acetylcholinesterase activity in a concentration-dependent manner. The histopathological aspect was marked especially with the infiltration of coelomic cells which confirms our biochemical findings. Our study provided novel insights to create a link between redox status and fatty acid composition disruptions to better understand ACRtriggered toxicity.