CONTEXT: The association between myofascial temporomandibular disorder (TMD) and nonrestorative sleep supports the investigation of therapies that can modulate the sleep/wake cycle. In this context, melatonin becomes an attractive treatment option for myofascial TMD pain. OBJECTIVES: To investigate the effects of melatonin on pain (primary aim) and sleep (secondary aim) as compared with placebo in a double-blind, randomized, parallel-group trial. METHODS: Thirty-two females, aged 20-40 years, with myofascial TMD pain were randomized into placebo or melatonin (5mg) treatment groups for a period of four weeks. RESULTS: There was a significant interaction (time vs. group) for the main outcomes of pain scores as indexed by the visual analogue scale and pressure pain threshold (analysis of variance; P<0.05 for these analyses). Post hoc analysis showed that the treatment reduced pain scores by -44% (95% CI -57%, -26%) compared with placebo, and it also increased the pressure pain threshold by 39% (95% CI 14%, 54%). The use of analgesic doses significantly decreased with time (P<0.01). The daily analgesic doses decreased by -66% (95% CI -94%, -41%) when comparing the two groups. Additionally, melatonin improved sleep quality, but its effect on pain was independent of the effect on sleep quality. CONCLUSION: This study provides additional evidence supporting the analgesic effects of melatonin on pain scores and analgesic consumption in patients with mild-to-moderate chronic myofascial TMD pain. Furthermore, melatonin improves sleep quality but its effect on pain appears to be independent of changes in sleep quality.