The measurement of dynamic changes in brain hemodynamic and metabolism events following head trauma could be valuable for injury prognosis and for planning of optimal medical treatment. Specifically, variations in blood flow and oxygenation levels serve as important biomarkers of numerous pathophysiological processes. We employed the dual-wavelength laser speckle imaging (DW-LSI) technique for simultaneous monitoring of changes in brain hemodynamics and cerebral blood flow (CBF) at early stages of head trauma in a mouse model of intact head injury (). For induction of head injury, we used a weight-drop device involving a metal mass () striking the mouse’s head in a regulated manner from a height of . In comparison to baseline measurements, noticeable dynamic variations were revealed immediately and up to 1 h postinjury, which indicate the severity of brain damage and highlight the ability of the DW-LSI arrangement to track brain pathophysiology induced by injury. To validate the monitoring of CBF by DW-LSI, measurements with laser Doppler flowmetry (LDF) were also performed (), which confirmed reduction in CBF following injury. A secondary focus of the study was to investigate the effectiveness of hypertonic saline as a neuroprotective agent, inhibiting the development of complications after brain injury in a subgroup of injured mice (), further demonstrating the ability of DW-LSI to monitor the effects upon brain dynamics of drug treatment. Overall, our findings further support the use of DW-LSI as a noninvasive, cost-effective tool to assess changes in hemodynamics under a variety of pathological conditions, suggesting its potential contribution to the biomedical field. To the best of our knowledge, this work is the first to make use of the DW-LSI modality in a small animal model to (1) investigate brain function during the critical first hour of closed head injury trauma, (2) correlate between injury parameters of LDF measurements, and (3) monitor brain hemodynamic and metabolic response to neuroprotective drug treatment.