The aim this study was to compare the deleterious effects caused by experimental hyposalivation, periodontitis, and the combination of both on periodontal tissues and mandibular biomechanics in rats. Hyposalivation (group H) was induced through bilateral submandibulectomy. Periodontitis (group EP) was induced by injecting LPS (1 mg/ml) into the gingiva of the first lower molars. A third group was subjected to both conditions (group H+EP). Alveolar bone loss was evaluated by micro-computed tomography and histomorphometric analysis, and gingival inflammatory mediators were assessed by specific techniques. Biomechanical properties were evaluated in mandible. Alveolar bone loss increased similarly in groups H, EP and H+EP compared to control. Metalloproteinase (MMP2 and MMP9) activity was similar in H and control, but higher in groups EP and H+EP (MMP2: C 9644+2214, EP 34441+3336, H 5818+1532, H+EP 42673+3184; MMP9: C 5792+961, EP 14807+861, H 9295+520, H+EP 4838+1531). The rest of the inflammatory mediators evaluated increased in groups H, EP and H+EP to a greater or lesser extent with respect to the control, although in most cases, they were higher in groups EP and H+EP than in group H. The biomechanical properties of the mandible increased in group H compared to the other three groups. Both hyposalivation and periodontitis cause periodontal damage, but hyposalivation also produces biomechanical alterations, causing more extensive deleterious effects than periodontitis.