Rationale: It is known that glucose administration is capable of improving performance on tests of declarative verbal memory and non-mnemonic tasks requiring high 'mental effort'. At the same time, cognitively demanding tasks are associated with elevated heart rate, a response that could feasibly be part of a physiological mechanism serving to increase the delivery of glucose to active brain substrates. Objective: The present placebo- controlled, double-blind, balanced, crossover study examined the interaction between glucose administration, cognitive performance and heart rate during three tasks of differing mental demand and somatically-matched control tasks. Methods: The effects of a glucose drink on participants' performance on two serial subtraction tasks (Serial Threes and Serial Sevens) and a Word Retrieval (Verbal Fluency) task were assessed. Heart rates were monitored throughout the experiment, and participants rated each task in terms of its perceived mental demand. Results: Serial Sevens was rated as the most mentally demanding task, followed by Word Retrieval, then Serial Threes. Glucose consumption significantly improved performance on Serial Sevens, with a trend for improved performance on Word Retrieval. Both Serial Sevens and Serial Threes were associated with significant heart rate elevation above that seen in somatically matched control tasks (ruling out the possibility that accelerated heart rate was due to peripheral mechanisms alone). Unexpectedly, participants in the glucose condition had higher heart rates during cognitive processing. Additionally, individuals whose baseline heart rates were below the median performed better on Serial Threes and Serial Sevens. Conclusion: We suggest that supplemental glucose preferentially targets tasks with a relatively high cognitive load, which itself (through unknown mechanisms) mobilises physiological reserves as part of a natural response to such tasks. Furthermore, baseline heart rate and responses to cognitive demand and glucose administration may represent important physiological individual differences.