The nocturnal peak of melatonin can be altered after anesthesia and surgery. We aimed to examine the melatonin levels during the day and night after anesthesia with three commonly used inhalational anesthetics. Forty-eight male Wistar albino rats were randomized into eight groups. Rats were administered anesthesia between 7:00 AM and 1:00 PM (day groups) or 7:00 PM and 1:00 AM (night groups) for 6 hours. At the end of the anesthesia, blood samples were collected for assessing melatonin levels. Mean values of melatonin levels after 6 hours of anesthesia during daytime were 43.17 +/- 12.95 for control, 59.79 +/- 27.83 for isoflurane, 50.75 +/- 34.28 for sevoflurane and 212.20 +/- 49.56 pg/mL for desflurane groups. The night groups' mean melatonin levels were 136.12 +/- 33.20 for control, 139.85 +/- 56.29 for isoflurane, 117.48 +/- 82.39 for sevoflurane and 128.70 +/- 44.63 pg/mL for desflurane groups. Desflurane anesthesia between 7:00 AM and 1:00 PM significantly increased melatonin levels (p < 0.001). Sevoflurane and desflurane anesthesia between 7:00 PM and 1:00 AM decreased the melatonin levels but there were no significant differences (pZ0.904 and p > 0.99, respectively). Isoflurane anesthesia did not significantly change melatonin levels during day or night (p = 0.718 and p > 0.99, respectively). Our results demonstrate that during daytime desflurane anesthesia can alter melatonin levels. Altered melatonin rhythm following inhalational anesthesia can be related to sleep disorders observed after anesthesia. Copyright (C) 2016, Kaohsiung Medical University. Published by Elsevier Taiwan LLC.