Glucose metabolism and energy expenditure are altered during rapid eye movement (REM) sleep. To understand this mechanism, it was hypothesized that the enzymes involved in the metabolism of glucose, viz. hexokinase and glucose-6-phosphatase, are affected by REM sleep deprivation. The flower pot technique was used for 1-, 2- and 4-day periods of REM sleep deprivation. Suitable control experiments were carried out to rule out the nonspecific effects. The results showed that glucose-6-phosphatase was first to be affected, and it showed decreased activity. In longer periods of deprivation, there was an increase in hexokinase activity. Both the altered enzyme activities returned to baseline level on recovery from REM sleep deprivation. Control experiments suggest that alterations were primarily caused by REM sleep deprivation, not nonspecific effects.