Avoiding secondary injury is of paramount importance in managing traumatic brain injury (TBI). Cerebral ischemia and hypoxia should be avoided. Hypotension and oxygen desaturation should be treated. The goal is to maintain adequate oxygen delivery to the brain to meet the rate of oxygen consumption by the brain (CMRO2). The choice of fluid should fulfill this utmost goal by augmenting oxygen delivery to the brain. Non-blood fluid, such as crystalloid and colloid, may help to treat hypotension and increase cerebral perfusion pressure (CPP), thus increase cerebral blood flow (CBF); however, it does not increase blood hemoglobin concentration and may actually decrease blood oxygen content due to hemodilution. Hypotonic, low sodium and dextrose-containing fluids should be avoided. 0.9% normal saline (NS) or even 3% NS should be considered if a crystalloid is chosen. The use of albumin in trauma victims is controversial. Most trauma centers choose not to use it. Mannitol is often adopted to decrease brain water and augment intravascular volume in patients with increased intracranial pressure. Red blood cell transfusion not only increases intravascular volume and facilitate CPP management but also augment blood oxygen content via the increase in hemoglobin. Other blood component such fresh frozen plasma, platelet, or cryoprecipitate, should be considered based on clinical situation. Unfortunately, the end point of fluid therapy, which is the match between oxygen delivery to the brain and oxygen consumption by the brain, is not easy to be monitored clinically. The choice of which fluid to be used and how much to be used is a decision based on patient’s clinical condition and good understanding of the pathophysiological effects of the fluid being chosen.