Introduction: Long-distance running race is a stressful event that can significantly affect virtually any of the physiologic systems of runners. More recently evidence has been mounting to support the long-distance running perception that athletes are susceptible to certain illness during intense training and major competition. Aim of Work: To focus on the immune function and neuroendocrine parameters response to prolonged (90 min) and intensive endurance running. Materials and Methods: Blood samples were collected from 12 male children runners (13.51 ± 1.29 years) 0h, 1hour, after the race. Complete blood count, secretion of cytokines in mitogen-activated cell culture and plasma, plasma concentration of β-endorphin, adrenocorticotropic hormone (ACTH), cortisol, and growth hormone (GH) were analyzed. Results: Significant increase in granulocyte and monocytes (MID-cell) count and lymphopenia were seen immediately after the race. Secretion of interleukin2 (IL-2) and interferon (IFN-γ) significantly declined at 0h and 1h after the running. Secretion of Tumor Necosis Factor (TNF-α) declined at 0h & remained suppressed until 1hours. Suppression in the secretion of (IL-1β) was observed at 1hour. Activated secretion of (IL-6) decreased after 1hours. Peak concentrations of ACTH, cortisol, β-endorphin, and GH were registered after the race (0 &1h). Conclusion: We co-ncluded that long-distance running race associated stress factors can alter physiologic balan-ce of cell-mediated versus humoral and antiinflammatory versus proinflammatory cytokin-es. Results suggest that hypothalamicpituitary-adrenocortical axis hormones played a sign-ificant role in the regulation of the observed changes. This information may be beneficial for development of new stress countermeasures to preserve wellness in subjects undergoing intensive physiological stress.