Perceived changes in occlusion and decreased range of motion are often expressed by patients with masticatory muscle pain. The adverse loading of craniomandibular tissues that results from an inadequate maxillomandibular relationship in combination with the coexisting dysfunction is widely regarded as the cause of pain. This study was designed to test whether pain can cause significant changes in position of the mandible and therefore form the basis for any perceived changes in the maxillomandibular relationship. A second objective was to determine whether pain can cause changes in the mandibular range of motion. Five subjects who rated pain intensity on a visual analog scale were used in a single-blind, randomized, repeated-measures study design. Tonic muscle pain was induced by infusion of 5% hypertonic saline solution into the central portion of the superficial masseter muscle. Isotonic saline solution was used as a control, with subjects blinded to the type of substance given. The effect of pain on the position of the apex of the gothic arch tracing, the direction of the lateral mandibular border movements, and the mandibular range of motion was studied in a horizontal plane with minimal occlusal separation. Pain significantly affected the position of the apex of the gothic arch tracing in anterior (F = 11.46, p = 0.03) and transverse (F = 35.0, p = 0.004) directions. Similarly, pain affected the orientation of the mandibular lateral border movements (F = 12.44, p = 0.02) and their magnitude (F = 14.97, p = 0.01). All pain-induced effects proved to be reversible. The observed effect of pain can explain the perceived change of bite that is frequently noted by patients with orofacial pain. This study provided evidence of an alternative causal relationship between pain and changes in occlusal relationship and questions occlusal therapy as treatment, directed toward the elimination of the underlying cause in patients with masticatory muscle pain.