The lowered CSF glucose concentration is the result of defective glucose transport into the CSF and the increased utilization of glucose in the brain. The CSF glucose depends on the blood glucose concentration. A CSF glucose of <40% of the blood glucose is considered abnormally low.

Glucose is an essential substrate for the metabolism of most cells. Because glucose is a polar molecule, transport through biological membranes requires specific transport proteins. GLUT-1 was one of the first glucose transporters reported. It is widely distributed in the endothelial tissues of the blood–brain barrier, making it responsible for the glucose uptake required by the tissues to sustain normal respiration in all cells.

Glucose is usually present in the CSF; the level is usually 60% that of the peripheral circulation. To appropriately judge the relative normality of the glucose concentrations, a simultaneous measurement of serum glucose (especially if the CSF glucose level is likely to be low) is recommended. Reduced CSF glucose levels can indicate fungal, tuburculous, or pyogenic infections; lymphomas; leukemia spreading to the meninges; meningoencephalitic mumps; or hypoglycemia. This low CSF glucose level associated with bacterial infection is probably due to enzymatic inhibition rather that actual bacterial consumption of the glucose. A decreased CSF glucose concentration is usually present in purulent meningitis. It has little value beyond supporting a diagnosis because the important information is derived from the CSF culture results.