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The main goal of this study was to investigate the seasonal chemical changes of two sea cucumber species caught from Portugal. The potential contribution to human health of lipids was also evaluated. For this, the chemical composition (protein, ash, and fat) and lipids composition of Holothuria arguinensis and Holothuria forskali was followed in summer and winter. Both species presented adequate levels of protein and ash and low content of total lipids, although their lipid profile showed a high proportion of polyunsaturated fatty acid (PUFA). Eicosapentaenoic acid (EPA) was abundant in all samples, and a favorable and similar n-3/n-6 ratio was found for both species. The atherogenic and thrombogenicity indices and ypocholesterolaemic/hypercholesterolaemic ratio suggests a high-quality for H. arguinensis and H. forskali. In general, significant differences were observed between species but not between summer and winter. Some significant variations were observed between summer and winter in the lipid profile of both species and in the chemical composition of H. forskali. Results indicate that these species have adequate nutritional quality for human consumption and may be suitable for the development of reliable fatty acid guides in sea cucumbers.