Monkeypox virus infection is characterized by a prodromal illness with fever, intense headache, lymphadenopathy, back pain, myalgias, and asthenia, followed by the eruption of skin lesions. A case series has reported monkeypox virus infection with primary anogenital and facial cellulitis. In addition, superimposed bacterial infections have been reported in several case reports. We present a monkeypox virus infection case of a patient presenting with jaw swelling initially thought to be secondary to cellulitis/abscess collection.A 25-year-old homosexual male on HIV pre-exposure prophylaxis presented to an urgent care center with a painful, ruptured, crusted chin lesion. Given recent contact with monkeypox virus-infected patients, a monkeypox swab was collected. He then developed a fever, jaw/neck swelling, and difficulty swallowing, which prompted him to come to our emergency department. He was febrile and tachycardic on presentation. The labs were unremarkable. A CT scan of the neck showed soft tissue thickening within the submental and submandibular regions bilaterally, consistent with cellulitis without evidence of abscess formation. It also showed prominent bilateral submandibular and left station IIA lymphadenopathy. We started the patient on intravenous ampicillin-sulbactam, but his swelling worsened. We suspected abscess formation clinically; however, a percutaneous drainage attempt yielded a dry tap. We added vancomycin for extra coverage, but the patient remained febrile, and his swelling continued to worsen. In the meantime, his monkeypox virus polymerase chain reaction (PCR) swab result returned positive, and he developed other skin lesions. These two findings and the lack of improvement with antibiotic therapy led us to believe that his fever was secondary to monkeypox and the swelling was secondary to reactive lymphadenopathy over true cellulitis. We stopped his antibiotics, and his symptoms improved with a complete resolution of the jaw swelling.This case was challenging to manage as the patient’s swelling was initially thought to be secondary to cellulitis and abscess collection, but it turned out to be secondary to lymphadenopathy. This case illustrates the significance and severity of lymphadenopathy in monkeypox virus infection, which can be initially misdiagnosed as cellulitis.