Growing evidence suggests a bidirectional communication between the central nervous system and immune system concerning sleep. Some studies suggest the presence of a relationship between the lack of sleep and the changes in immune functions and inflammatory profile. However, knowledge about the effect of sleep deprivation on the immune system is limited and the results are contradictory. The objective of this study is to investigate the effect of sleep deprivation and obstructive sleep apnea (OSA) on: the functions of neutrophils (phagocytosis and production of reactive oxygen species (ROS), the levels of T helper (Thl) and Th2 cytokines and chemokines and the ex vivo proliferative patterns of T-cells (CD4 & CD8), natural killer (NK) cells (CD8+ & CD8-) and NKT cells. We enrolled in this study a total of 22 sever OSA patients, 21 healthy volunteers who slept 7 to 8 hrs/day for one week and 8 healthy volunteers who slept 7 to 8 hrs/day during the first week, 5 hrs/day during the second week and 7 to 8 hrs/day during the third week. Levels of the different cytokines and cortisol were measured in patient's serum using cytometric beads array (CBA) and enzyme-linked immunosorbent assay (ELISA), respectively. Neutrophils functions were measured using phagocytosis assay and nitroblue-tetrazolium (NBT) test. The proliferative capacity of T-cells, NK cells and NKT cells was analyzed using flow cytometry. Our data showed increased IL-1B levels in OSA patients. These levels significantly correlated with the increase in the percentage of CD4 T-cells in these patients (p = 0.038). In addition, there was an increase in the levels of IL-6 (p = 0.004) and CXCL 9 (p = 0.028) during sleep deprivation, while a decrease in the levels of IFN-Y (p = 0.008) in OSA patients was noted. Moreover, phagocytosis and ROS production were reduced in both OSA patients and during sleep deprivation. Interestingly, the decrease in the ROS production correlated directly with the decrease in phagocytosis in patients with OSA (p = 0.01). Finally, there was a decrease in the CD4 T-cells population during sleep deprivation (p = 0.017) and an increase in the proliferative potential of NK cells in OSA patients (p = 0.007). Our results indicate that sleep deprivation and OSA alter the immune functions. This altered pattern of the immune functions occurred independently of the presence of cortisol.