The chapter discusses the regulatory influence of sleep and the circadian system on immune functions. It highlights that immune parameters such as the numbers of naïve T cells and pro-inflammatory cytokines peak during early nocturnal sleep, while circulating numbers of cytotoxic natural killer cells and anti-inflammatory cytokine activity peak during daytime wakefulness. Studies comparing nocturnal sleep with 24-hour periods of wakefulness suggest that sleep facilitates the extravasation of T cells and their redistribution to lymph nodes, enhancing the interaction between antigen-presenting cells and T helper cells, particularly interleukin-12. Sleep also plays a crucial role in forming immunological memory, especially during slow wave sleep, characterized by a pro-inflammatory endocrine milieu with high growth hormone and prolactin levels and low cortisol and catecholamine concentrations. The chapter emphasizes the bidirectional communication between the nervous and immune systems, with shared signals and key players, and explores the impact of sleep on immune cell dynamics, cytokine production, and immune function. It concludes that sleep selectively modulates certain leukocyte subsets, promoting pro-inflammatory cytokine production and supporting adaptive immune responses, while also influencing the activity of natural regulatory T cells to maintain immune homeostasis.The chapter discusses the regulatory influence of sleep and the circadian system on immune functions. It highlights that immune parameters such as the numbers of naïve T cells and pro-inflammatory cytokines peak during early nocturnal sleep, while circulating numbers of cytotoxic natural killer cells and anti-inflammatory cytokine activity peak during daytime wakefulness. Studies comparing nocturnal sleep with 24-hour periods of wakefulness suggest that sleep facilitates the extravasation of T cells and their redistribution to lymph nodes, enhancing the interaction between antigen-presenting cells and T helper cells, particularly interleukin-12. Sleep also plays a crucial role in forming immunological memory, especially during slow wave sleep, characterized by a pro-inflammatory endocrine milieu with high growth hormone and prolactin levels and low cortisol and catecholamine concentrations. The chapter emphasizes the bidirectional communication between the nervous and immune systems, with shared signals and key players, and explores the impact of sleep on immune cell dynamics, cytokine production, and immune function. It concludes that sleep selectively modulates certain leukocyte subsets, promoting pro-inflammatory cytokine production and supporting adaptive immune responses, while also influencing the activity of natural regulatory T cells to maintain immune homeostasis.