Whole sesame seeds (WSS) are good source of linoleic acid (LA) and lignans the effect of which have not been studied on the expression of key- genes in monocytes of dairy goats. Twenty-four, F2 crossbred [Alpine × Local (Greek) breeds] dairy goats (BW = 44.9 ± 5.4 kg), age (3–4 years old),were divided into three homogenous subgroups; the control group (CON) in which no WSS included and the two treated groups in the concentrates of which WSS were included at 5 % (WSS5) and 10 % (WSS10) respectively, by partially substituting both soybean meal and corn grain. The findings indicated a significant increase in the expression level of the IRF3 gene in the monocytes of goats fed with WSS5 compared to the CON group, throughout the experimental period. Both dietary inclusion levels of WSS caused a numerical downregulation in the expression levels of TNFA, IFNG, CCL5, and IL8. Additionally, the WSS10 group exhibited a numerical decrease in the expression levels of TLR4, IL1A, and IL1B compared to the other groups. Consequently, this study revealed that the inclusion of WSS in the above levels in goats’ diets does not modify pro-inflammatory signaling pathways or the expression patterns of genes. The lignans of WSS ensure the safe administration of their linoleic acid when these included at 5 % (WSS5) and 10 % (WSS10) of the concentrates in goats’ diets.