The role of sympathetic and parasympathetic activity in relation to the repetitive exposure to static stretching (SS) on heart and musculoskeletal hemodynamics in stretched and resting muscles is still a matter of debate. The aim of the study was to determine cardiac and musculoskeletal hemodynamics to repetitive bouts of unilateral SS. Sympathetic and parasympathetic activity contribution to the central hemodynamics and local difference in circulation of stretched and resting muscles were also investigated. In eight participants, heart rate (HR), cardiac output (CO), mean arterial pressure (MAP), HR variability (HRV), blood pressure variability (BPV), and blood flow in passively stretched limb (SL) and control (CL, resting limb) were measured during five bouts of unilateral SS (45 s of knee flexion and 15 s of knee extension). SS increased sympathetic (~20%) and decreased parasympathetic activity (~30%) with a prevalence of parasympathetic withdrawal. During SS, HR, CO, and MAP increased by ~18 beats/min, ~0.29 l/min, ~12 mmHg, respectively. Peak blood flow in response to the first stretching maneuver increased significantly (+377 ± 95 ml/min) in the SL and reduced significantly (−57 ± 48 ml/min) in the CL. This between-limb difference in local circulation response to SS disappeared after the second SS bout. These results indicate that heart hemodynamic responses to SS are primarily influenced by the parasympathetic withdrawal rather than by the increase in sympathetic activity. The balance between neural and local factors contributing to blood flow regulation was affected by the level of SS exposure, likely associated with differences in the bioavailability of local vasoactive factors throughout the stretching bouts. NEW & NOTEWORTHY Repetitive exposure to static stretching (SS) on heart and musculoskeletal hemodynamics in stretched and remote muscles may be influenced by neural and local factors. We documented that SS-induced heart hemodynamic responses are primarily influenced by parasympathetic withdrawal. The balance between neural and local factors contributing to the regulation of musculoskeletal hemodynamics is dependent on SS exposure possibly because of different local vasoactive factor bioavailability during the subsequent stretching bouts.