Sleep deprivation (SD) has enriched our treatment programme for major depression. SD has been demonstrated to modify different host defence activities. There is some evidence that there are reciprocal relationships between immune function and increased hypothalamic-pituitary-adrenocortical (HPA) axis activity in depression. We therefore investigated the number of leukocytes, granulocytes, monocytes, lymphocytes, B cells, T cells, helper T cells, cytotoxic T cells, NK cells and salivary cortisol in 10 healthy men before and after total SD (TSD) as well as after recovery sleep. Blood samples were drawn on 3 consecutive days at 7 am, 1 pm and 7 pm, respectively. Comparison of the 7 am values by contrast analysis yielded significant differences for granulocytes (p = 0.044) and NK cells (p = 0.001) after SD and recovery sleep. NK cells decreased and granulocytes increased after SD and after recovery sleep. Significant differences between single points in time across the day were found for granulocytes (p = 0.022), monocytes (p = 0.031), T cells (p = 0.005), helper T cells (p = 0.004), cytotoxic T cells (p = 0.005) and NK cells (p = 0.017). No significant difference could be detected for leukocytes, lymphocytes and B cells counts. These results favour the thesis that SD and recovery sleep lead to changes in the distribution of peripheral leukocytes, especially in a reduction of NK cells after SD and recovery sleep. The cortisol rhythm was affected neither by SD nor recovery sleep.