Background: Down syndrome (DS) is a genetic disorder, which is associated with various manifestations including neuromuscular defects. These defects should be compensated through other pathways for regeneration and repair, with growing evidence suggest that circulating neural and muscle progenitor cells have pivotal role in the maintenance of muscle and neural tissues integrity and repair after injury. Objective: The aim of the present work was to determine factors and markers of muscle and neural regeneration in the blood of Down syndrome (DS) patients as well as controls and demonstrating correlation between them. Subjects and Methods: This study was carried out on 40 DS patients and 30 apparently healthy controls. DS patients were selected from cases already diagnosed by chromosomal karyotyping in the genetic unit, pediatric department, Cairo University. Factors of regeneration were measured in terms of NGF, SDF-1 and Galectin-1 using ELISA. Markers of regeneration were measured in terms of circulating mononuclear cells expressing Nestin, CD34 and CD45 using flow cytometry. Results: Results showed significant increase in plasma NGF,SDF-1, and Gal-1 in DS patients compared to controls. On the other hand, we demonstrated significant decrease in Nestin, CD34, and CD45 surface marker. Our results showed negative correlation between NGF and Nestin, between SDF-1 and CD34, and between Gal-1 and CD45 among DS patients. Conclusion: The significant increase in the NGF, SDF-1 and Gal-1 accompanied by a significant decrease in number of mononuclear cells expressing, Nestin, CD34 and CD45 indicated neuromuscular degeneration in DS, which was not compensated by the regenerative mechanism.