The nervous and immune techniques are intricately linked1. Though psychological stress is thought to modulate immune operate, mechanistic pathways linking stress networks within the mind to peripheral leukocytes stay poorly understood2. Right here, we present that distinct mind areas form leukocyte distribution and performance all through the physique throughout acute stress in mice. Utilizing optogenetics and chemogenetics, we display that motor circuits induce speedy neutrophil mobilization from the bone marrow to peripheral tissues by way of skeletal muscle-derived neutrophil-attracting chemokines. Conversely, the paraventricular hypothalamus controls monocyte and lymphocyte egress from secondary lymphoid organs and blood to the bone marrow via direct, cell-intrinsic glucocorticoid signaling. These stress-induced, counter-directional, population-wide leukocyte shifts are related to altered illness susceptibility. On the one hand, acute stress adjustments innate immunity by reprogramming neutrophils and directing their recruitment to websites of harm. However, corticotropin releasing hormone (CRH) neuron-mediated leukocyte shifts shield in opposition to the acquisition of autoimmunity, however impair immunity to SARS-CoV-2 and influenza an infection. Collectively, these information present that distinct mind areas differentially and quickly tailor the leukocyte panorama throughout psychological stress, thus calibrating the immune system’s capability to reply to bodily threats.