Muscle satellite cell (SC) regulation is a complex process involving many key signaling molecules. Recently, the neurotrophin - brain-derived neurotropic factor (BDNF) has implicated in SC regulation in animals. To date, little is known regarding the role of BDNF in human SC function in vivo. Twenty-nine males (21±0.5y) participated in the study. Muscle biopsies from the thigh were obtained prior to a bout of 300 maximal eccentric contractions (PRE), and 6h, 24h, 72h, and 96h of post-exercise. BDNF was not detected in any quiescent (Pax7+/MyoD-) SCs across the time-course. BDNF co-localized to 39±5% of proliferating (Pax7+/MyoD+) cells at PRE, which increased to 84±3% by 96h (P<0.05). BDNF was only detected in 13±5% of differentiating (Pax7-/MyoD+) cells at PRE, which increased to 67±4% by 96h (P<0.05). The number of Myogenin+ cells increased 95% from PRE (1.6±0.2 cells/100MF) at 24h (3.1±0.3 cells/100MF) and remained elevated until 96h (cells/100MF), p<0.05. The proportion of BDNF+/Myogenin+ cells was 26±0.3% at PRE, peaking at 24h (49±3%, p<0.05) and remained elevated at 96h (p<0.05). These data are the first to demonstrate an association between SC proliferation and differentiation and BDNF expression in humans in vivo, with BDNF co-localization to SCs increasing during the later stages of proliferation and early differentiation. Novelty: • BDNF is associated with SC response to muscle injury • BDNF was not detected in non-activated (quiescent) SCs • BDNF is associated with late proliferation and early differentiation of SCs in vivo in humans.