Background <p>Mandibular osteomyelitis is a clinically relevant condition in South American camelids (SACs). It is most commonly reported secondary to dental disease. Information on primary mandibular osteomyelitis without dental involvement remain scarce in these species. This case series reports the clinical presentation, diagnostic findings, treatment, and outcome of four SACs diagnosed with severe mandibular osteomyelitis in the absence of primary dental disease.</p> Case presentation <p>Four SACs (three alpacas and one llama) presented with either unilateral or bilateral mandibular swelling and ventral draining tracts. Oral examination revealed mandibular bone thickening and purulent fistulae in close proximity to the cheek teeth, however, none of the teeth showed clinical abnormalities, like purulent discharge from their gingival sulci or abnormal mobility upon oral examination.</p> <p><?noindent??>Computed tomography (CT) was performed in all cases and demonstrated extensive osteolytic lesions of the mandibular body, marked periosteal reaction, multiple osseous sequestra, and varying degrees of surrounding soft tissue swelling. CT-findings did not indicate primary dental involvement like signs of apical infection, although some periodontal changes could be observed.</p> <p><?noindent??>Treatment primarily consisted of aggressive surgical debridement, removal of sequestrated bone without dental extraction, and short courses of systemic antimicrobial and anti-inflammatory therapy.Repeated follow-up examinations enabled further debridement when necessary and promoted progressive healing. Clinical outcomes were favorable, with long-term resolution of clinical signs reported in most animals while preserving clinically normal teeth.</p> Conclusions <p>This case series highlights that severe mandibular osteomyelitis can occur independently of dental disease in SACs. Computed tomography proved essential for accurate diagnosis and surgical planning, and successful treatment relied mainly on thorough surgical debridement rather than prolonged antimicrobial therapy.</p> <p><?noindent??>These findings emphasize the importance of advanced imaging and proper follow-up care when mandibular osteomyelitis is present in these animals. Preservation of nearly all clinically healthy teeth was possible in these cases and may be advantageous for maintaining long-term masticatory function. Further research is required to elucidate underlying pathogenesis and identify potential preventative measures.</p>