Sleep disturbance in neurological and psychiatric disorders is common and associated with diminished cognitive functioning. Whilst these deficits can be localised predominantly to frontal and parietal regions, there have been reported inconsistencies which may be due to differences in the difficulty and type of task. In the present study we examined the effects of sleep deprivation (SD) whilst parametrically varying working memory load using an n-back task. 20 right-handed males performed the n-back task after a night of normal sleep (RW: rested wakefulness) and after approximately 31. h of SD. Comparison of load responsive cerebral activation identified two clusters where the parametric response was altered after SD. In the right ventrolateral prefrontal cortex activity was reduced at the most difficult working memory load, whereas in the right inferior parietal lobe activity was increased at the simplest working memory load. The strength of activation in both of these regions during RW predicted the response of those same regions to SD. While the ability to predict signal change has previously been demonstrated using behavioural measures, to our knowledge this is the first study to show that the neuronal effects of SD can be predicted based upon activation during a normal rested condition.