Previous research has identified that glucose administration can enhance cognitive performance, especially during more intense cognitive processing. There appears to be a reciprocal relationship between falling glucose levels and cognitive performance, particularly under conditions of cognitive demand. The present placebo-controlled, double-blind, balanced, crossover study examined the possibility that a high cognitive load may produce changes in blood glucose levels. A secondary aim was to examine the effects of glucose on tasks of varying cognitive demand load. The effects of a glucose drink on participants' performance of a serial subtraction task (computerised Serial Sevens), a somatically matched control task (key-pressing), a short interval Word Memory task and a Word Retrieval (Verbal Fluency) task were assessed. The change in blood glucose during the demanding computerised Serial Sevens was compared to the change occurring during the key-pressing control. Glucose consumption significantly improved performance on Serial Sevens, with a trend for improved performance on Word Retrieval and no effect on the Word Memory task. Compared with the control task, Serial Sevens resulted in a significant reduction in blood glucose in both drink conditions. This accelerated decay was significantly greater following glucose than placebo. It is suggested that the amount of cognitive load associated with task performance is an index of its sensitivity to enhancement by glucose. Furthermore, a period of intense cognitive processing leads to a measurable decrease in levels of peripherally measured blood glucose, which may be linked to increased neural energy expenditure. However, the relative contribution of central and peripheral (e.g. cardiac) activity to this effect has yet to be determined.