CASE DESCRIPTION 2 female red-necked wallabies (Macropus rufogriseus) were evaluated because of sudden-onset mandibular swelling, ptyalism, and hyporexia. CLINICAL FINDINGS Physical examination revealed a mandibular swelling with a fluctuant center in both wallabies. Hematologic analysis revealed leukocytosis with a mature neutrophilia and monocytosis in one wallaby (case 1) and a slight neutrophilia, hyperglobulinemia, and high serum alanine aminotransferase activity in the other (case 2). Cytologic examination of the swelling revealed a uniform population of gram-negative rods in case 1 and neutrophilic inflammation in case 2. Radiography revealed a soft tissue mandibular swelling with osteolucency around mandibular incisor roots in both wallabies. Computed tomography revealed changes consistent with chronic active mandibular osteomyelitis and reactive bone formation, but also sequestra formation not appreciable via radiography. TREATMENT AND OUTCOME Long-term antimicrobial treatment was initiated with clindamycin (17 to 21 mg/kg [7.7 to 9.5 mg/lb], IV, q 12 h for 40 to 55 days) and high-dose benzathine penicillin G (80,000 U/kg [36,364 U/lb], SC, q 12 h for 150 days). Serial CT was performed to evaluate response to treatment and resolution of disease. A CT scan 18 months after the initial evaluation revealed complete resolution of osteomyelitis and sequestra. CLINICAL RELEVANCE Advanced imaging and long-term treatment and management were integral to the successful outcome for these wallabies, given that the osseous changes visible on CT images were not visible on standard radiographs, guiding therapeutic decision-making. This report provides new therapeutic and diagnostic monitoring information to assist clinicians with similar cases.