The results of the present study show that subjects who received an overnight infusion of isotonic fluid did significantly less well at particular neuropsychological tests than controls who did not receive such an infusion. The relevant test parameters involved aspects of word list learning, and concept shifting on a complex speed task. Potentially biasing factors such as anxiety, disturbed sleep, education and age could be discarded. With respect to the physiological mechanism involved, the results suggest that a relatively expanded extracellular volume without dilutional hyponatremia might underlie the diminished performance. The experimental group did not lose weight overnight, and the hemoglobin and haematocrit level of the experimental group were significantly different from those of the control group; the blood pressure, plasma electrolytes and osmolality were not different. The present results provide evidence that disturbances in fluid homeostasis may affect cognitive performance.