Dietary lipids could modify fatty acid (FA) composition in fish tissues. Long chain polyunsaturated fatty acids (LC-PUFAs) such as arachidonic acid (ARA), eicosapentaneoic acid (EPA) and docosahexaenoic acid (DHA) are able to modulate the immune status in fish through an inflammatory process but their availability may be limited when fish are exclusively fed plant oils. This study was conducted to evaluate how to maximise the utilisation of dietary plant oil for an efficient inflammatory response in common carp head kidney leukocytes (HKLs) exposed to a gram-negative bacterial endotoxin, Escherichia coli lipopolysaccharides (LPS). HKLs were isolated from fish fed cod liver oil (CLO), linseed oil (LO), sesame oil (SO) a blend of SO and LO (SLO, v:v 1:1), and these plant oil diets supplemented with DHA (SO + DHA, SOD) or ARA (LO + ARA, LOA) for 6 weeks. Cells were then exposed to LPS at a dose of 10 μg/mL for 4 and 24 h. Peroxidase activity, total Ig, and NO levels were measured in the culture medium, while cells were used for expression analyses of candidate genes in pattern recognition (tlr-4), eicosanoid metabolism (pge2, 5-lox), pro-inflammatory (il-1, il-6, il-8, tnf-α, nf-kb, inos, cxc), anti-inflammatory (il-10, nf-kbi, tgf-β1) responses, and cytoprotective (gpx-1, prdx-3) processes. Results showed that LPS induced significantly inflammatory responses, evidenced by a high level of almost all the targeted humoral immune parameters and/or gene expression. Expression of inflammatory cytokines and other inflammatory mediators was upregulated after 4 h-LPS exposure and reverted to basal levels after 24 h. HKLs from fish fed SLO, LOA, or SOD diet exhibited a more efficient regulation of acute inflammatory processes than those fed CLO diet. The results indicate that the immune competence of fish fed plant oil mixture was comparable to the one of fish fed fish oil diet. Moreover, the supplementation of ARA or DHA induced similar immunomodulation in common carp.