Dysfunction of the autonomic nervous system (ANS) of the brain in sepsis can cause severe systemic inflammation and even death. Numerous data confirmed the role of ANS dysfunction in the occurrence, course, and outcome of systemic sepsis. The parasympathetic part of the ANS modifies the inflammation through cholinergic receptors of internal organs, macrophages, and lymphocytes (the cholinergic antiinflammatory pathway). The sympathetic part of ANS controls the activity of macrophages and lymphocytes by influencing β2-adrenergic receptors, causing the activation of intracellular genes encoding the synthesis of cytokines (anti-inflammatory beta2-adrenergic receptor interleukin-10 pathway, β2AR-IL-10). The interaction of ANS with infectious agents and the immune system ensures the maintenance of homeostasis or the appearance of a critical generalized infection. During inflammation, the ANS participates in the inflammatory response by releasing sympathetic or parasympathetic neurotransmitters and neuropeptides. It is extremely important to determine the functional state of the ANS in critical conditions, since both cholinergic and sympathomimetic agents can act as either anti- or pro-inflammatory stimuli.