Sleep deprivation is now recognized as an increasingly common condition inherent to modern society, and one that in many ways, is detrimental to certain physiologic systems, namely, immune function. Although sleep is now viewed by a significant body of researchers as being essential for the proper working of a host of defense systems, the consequences of lack of sleep on immune function remains to be fully comprehended. The aim of the current study was to investigate how paradoxical sleep deprivation (PSD) for 24 and 96 hours and sleep restriction (SR) for 21 days by the modified multiple platform method, and their respective 24h recovery periods, affect immune activation in rats. To this end, we assessed circulating white blood cell counts, lymphocyte count within immune organs as well as immunoglobulin (Ig) and complement production. The data revealed that PSD for 96h increased complement C3 and corticosterone concentration in relation to the control group. In contrast, the spleen weight, total leukocytes, and lymphocytes decreased during SR for 21 days when compared with the control group, although production of a certain class of immunoglobulin, the IgM, did increase. After recovery sleep, lymphocyte count in axillary lymph nodes grew when rats had rebound sleep after PSD for 24h, neutrophils increased after PSD96h and lymphocytes numbers were higher after SR21d. Such alterations during sleep deprivation suggest only minor alterations of nonspecific immune parameters during acute PSD, and a significant impairment in cellular response during chronic SR.