Spreading Depolarisations (SDs) occur spontaneously and frequently in injured human brain. They propagate slowly through injured tissue often cycling around a local area of damage. Tissue recovery after an SD requires greatly augmented energy utilisation to normalise ionic gradients from a virtually complete loss of membrane potential. In the injured brain this is difficult because local blood flow is often low and unreactive. In this study we use a new variant of microdialysis, continuous on-line microdialysis (coMD), to observe the effects of SDs on brain metabolism. The neurochemical changes are dynamic and take place on the timescale of the passage of an SD past the microdialysis probe. Dialysate potassium levels provide an ionic correlate of cellular depolarisation and show a clear transient increase. Dialysate glucose levels reflect a balance between local tissue glucose supply and utilization. These show a clear transient decrease of variable magnitude and duration. Dialysate lactate levels indicate non-oxidative metabolism of glucose and show a transient increase. Preliminary data suggest that the transient changes recover more slowly after the passage of a sequence of multiple SD’s giving rise to a decrease in basal dialysate glucose and an increase in basal dialysate potassium and lactate levels.