Background: Insufficient sleep alters the body’s physiological functions. This study investigated whether oxidative stress (OS) in the thalamus was correlated with the pain behaviour score in the rapid eye movement (REM) sleep-deprived rat model. Methods: Four groups of Sprague-Dawley rats were included in the study (n = 6): i) control; ii) REM sleep-deprived rats for 72 h (REMsd); iii) REM sleep-deprived rats for 72 h pretreated with Tualang honey (REMsd-H) and iv) tank control (TC). Following the intervention, 1% formalin was injected on the right hind paw and pain behaviour was recorded for 1 h. OS markers of glutathione (GSH), glutathione reductase (GR), superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) in the thalamus were measured. Results: REM sleep deprivation increased pain behaviour scores in phase II of the formalin test with decreased GSH, GR, SOD and CAT. The MDA level was significantly higher in the REMsd compared to REMsd-H. There was an inverse correlation between pain behaviour scores and GSH, GR and SOD levels. A positive correlation was found between the pain behaviour score and the MDA level. Conclusion: OS levels were significantly correlated with the pain behaviour score in the REMsd rats. Tualang honey administration reduced pain behaviour score and OS in the thalamus.