The present invention relates to methods and compositions that inhibit the effects of nitric oxide for inhibiting post-traumatic immunodepression. It is based, at least in part, on the discovery that, in a murine model system of trauma, genetic or chemical reduction of nitric oxide inhibited the development of immunodepression. Accordingly, the present invention provides for methods and compositions to be administered to subjects, post-trauma, that inhibit the effects of nitric oxide by inhibiting inducible nitric oxide synthase (iNOS) and/or scavenge nitric oxide.