Background: During intestinal inflammation tumour necrosis factor alpha (TNF-α) level is increased (Tabas et al. 2013) and also malabsorption of nutrients may occur. In this regard, we have previously demonstrated in Caco-2 cells that TNF-α inhibits sugar uptake by decreasing the amount of the Na+-glucose cotransporter SGLT1 in the plasma membrane (Barrenetxe et al. 2013). The omega-3 long-chain polyunsaturated fatty acids (n-3 PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and their lipid mediators resolvins (Rv), protectins and maresins (MaR), are able to counteract intestinal inflammation in models of Intestinal Bowel Disease (Barbalho et al. 2016; Chatterjee et al. 2014; Bento et al. 2014). The aim of the present study was to investigate in Caco-2 cells whether EPA, DHA and its derived lipid mediators RvD1, RvD2 and MaR1are able to block the inhibitory effect of TNFα on sugar transport and the implication of GPR120 on EPA and DHA action. Methods: Caco-2 cells were grown on culture plates and pre-incubated for 1 hour with TNF-α (10 ng/ml) and/or 100 µM EPA; 100 µM DHA; 100 nM RvD1; 100 nM RvD2 and 100 nM MaR1 before measuring the apical uptake of 0.1 mM α-methyl-glucoside (α-MG) for 15 min. The functional implication of GPR120 was investigated using its inhibitor AH7614 (100 µM). The expression of SGLT1 in Caco-2 cells brush border membrane vesicles, under the same experimental conditions used for the functional studies, was analysed by Western blot. Results: Both EPA and DHA prevented the inhibition of α-MG uptake induced by TNF-α. This effect was accompanied by the abolishment of SGLT1 intracellular recruitment by the cytokine. Likewise, RvD1, RvD2 and MaR1 blocked the TNF-α-induced decrease of sugar transport. The presence of the GPR120 inhibitor avoided the effects of EPA on TNF-α-induced inhibition of α-MG uptake, while did not significantly affect DHA action, suggesting that EPA produces its effects through GPR120, but DHA effect seems to be GPR120 independent. Conclusions: n3-PUFAs and its derived-lipid mediators can reverse the decrease on sugar uptake induced by TNF-α. Therefore, these molecules could be beneficial in patients that suffer malabsorption associated with intestinal inflammation.