Abstract  A study was conducted to investigate the effects of l-arginine (Arg) on performance and immune function in cyclophosphamide (CY) immunosuppressed weaned pigs. The weaned pigs were allotted randomly into one of three treatments, including: (1) non-challenged control; (2) CY-challenged group; and (3) CY + 0.5% Arg. On days 14 and 21 of the trial, pigs were injected with CY or sterile saline. Blood samples were obtained on days 21 and 28 of the trial for further analysis. On day 28, delayed-type hypersensitivity reaction was evaluated. Arg alleviated the decrease of average daily gain (P < 0.05) induced by CY challenge from days 21 to 28. Arg mitigated the CY-induced decrease of total white blood cell numbers (P < 0.05) on day 28 and improved the lymphocyte percentage on day 21 (P < 0.05). Arg increased the delayed-type hypersensitivity reaction (P < 0.05), and attenuated the decrease of bovine serum albumin antibody level caused by CY treatment (P < 0.05) on day 28. In addition, Arg elevated the levels of serum interleukin-2 and interferon-γ (P < 0.05) on day 28, and mitigated the decrease of serum interferon-γ level on day 21 (P < 0.05). These results indicate that Arg supplementation has beneficial effects in attenuating the immunosuppressive effects of CY challenge, therefore improving growth performance of young pigs.