We evaluated whether the nanoformulation of curcumin could be more effective than free curcumin against arsenic-induced immune dysfunction in rats. Curcumin was encapsulated in polylactic-co-glycolic acid (PLGA). Nanocurcumin (CUR-NP) exhibited a spherical shape with the mean particle size of 130.8 nm. Rats were randomly divided into five groups of six each. Group I was kept as the control. In Group II, rats were exposed to sodium arsenite (25 ppm) daily through drinking water for 42 days. Groups III, IV and V were treated with arsenic as in Group II, however, they were administered with nanoparticle, curcumin (100 mg/kg bw) and CUR-NP (100 mg/kg bw), respectively, by oral gavage during the last 14 days of arsenic exposure. At term, serum and spleen were collected. Immune dysfunction was evaluated by assessing cellular and humoral immunities. Arsenic significantly decreased the splenic lymphocyte proliferation in response to the antigen — Keyhole Limpet Hemocyanin (KLH) and mitogen — concanavalin-A. Arsenic reduced both the delayed type hypersensitivity response and secondary antibody (IgG) response to KLH. It also reduced the lipopolysaccharide-stimulated nitric oxide production in splenic lymphocytes. Free curcumin and CUR-NP treatment significantly attenuated these arsenic-mediated effects. However, the magnitude of the effects indicates that CUR-NP has better ameliorative potential than free curcumin at the equivalent dose level.