The expanding uses of carbon nanotubes (CNTs) in industry and medicine have raised concerns about their toxicity on human and animal health. CNTs, including multi-walled nanotubes (MWCNTs), have been reported to induce immunotoxic, inflammatory, and oxidative effects. Quercetin is a natural flavonoid present in many vegetables and fruits and has immunomodulatory, anti-inflammatory, and antioxidant properties. Herein, we investigated the protective effects of quercetin on pristine MWCNTs-induced immunotoxicity in mice. In comparison with two doses of MWCNTs, high doses [0.5 mg/kg body weight (BW), once intraperitoneally (IP)] caused higher immunotoxic, inflammatory, and oxidative effects than low doses (0.25 mg/kg BW, once IP). Administration of quercetin (30 mg/kg BW, IP for 2 weeks) relieved these deleterious effects as evidenced by (1) reduced spleen weight, (2) increased number of total leukocytes, lymphocytes, and neutrophils, (3) elevated serum levels of IgM, IgG, and IgA, (4) decreased lipid peroxide malondialdehyde levels and increased levels of antioxidant markers reduced glutathione, superoxide dismutase, and catalase in the spleen, (5) decreased concentrations and mRNA levels of inflammatory markers tumor necrosis factor-alpha (TNF), interleukin 1 beta (IL1ß), and IL6 in the spleen, (6) downregulated expression of immunomodulatory genes transforming growth factor-beta (TGFß), cyclooxygenase2 (COX2), and IL10, and (7) regenerative histological changes as indicated by decreased mononuclear cell infiltration, minimized degenerative changes and restored lymphocytes depletion in the spleen. These results infer that quercetin can ameliorate MWCNTs-induced immunotoxic, inflammatory, and oxidative effects.