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Small size excretory/secretory (ES) antigens of the <i>Haemonchus contortus</i> parasite have intense interest among researchers for understanding the molecular basis of helminths immune regulation in term of control strategies. Immunomodulatory roles of <i>H. contortus</i> ES-15 kDa (HcES-15) on host immune cells during host&#8722;parasite interactions are unknown. In this study, the HcES-15 gene was cloned and expression of recombinant protein (rHcES-15) was induced by isopropyl-&#223;-D-thiogalactopyranoside (IPTG). Binding activity of rHcES-15 to goat peripheral blood mononuclear cells (PBMCs) was confirmed by immunofluorescence assay (IFA) and immunohistochemical analysis showed that <i>H. contortus</i> 15 kDa protein localized in the outer and inner structure of the adult worm, clearly indicated as the parasite&#8217;s ES antigen. The immunoregulatory role on cytokines production, cell proliferation, cell migration, nitric oxide (NO) production, apoptosis, and phagocytosis were observed by co-incubation of rHcES-15 with goat PBMCs. The results showed that cytokines IL-4, IL-10, IL-17, the production of nitric oxide (NO), PBMCs apoptosis, and monocytes phagocytosis were all elevated after cells incubated with rHcES-15 at differential protein concentrations. We also found that IFN-&#947;, TGF-&#946;1, cells proliferation and migration were significantly suppressed with the interaction of rHcES-15 protein. Our findings indicated that low molecular ES antigens of <i>H. contortus</i> possessed discrete immunoregulatory roles, which will help to understand the mechanisms involved in immune evasion by the parasite during host&#8722;parasite interactions.