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Brazilian porcupine poxvirus (BPoPV) is a new poxvirus recently described in porcupines (Coendou prehensilis) from Brazil. Herein, we described a free-ranging adult male Coendou (Sphiggurus) spinosus rescued after being found lethargic on the ground in a rural area. The animal presented crusty, edematous, and suppurative skin lesions on the face, tail, and perineum, and yellowish ocular secretion. The diagnosis was performed by histopathology, transmission electron microscopy (TEM), PCR, and sequencing. Microscopically, proliferative and necrotizing dermatitis, subacute, multifocal with ballooning degeneration, and eosinophilic intracytoplasmic viral inclusion bodies were observed. TEM confirmed large brick-shaped virions inside the keratinocyte cytoplasm, measuring about 200-280 × 120-180 nm. Partial fragment of intracellular mature virion membrane protein gene and putative metalloproteinase gene was successfully amplified and sequenced, and the strain herein denoted IAL/21 V-102 was classified as BPoPV, showing 99.4% of nucleotide identity to the reference strain UFU/USP001. Enrofloxacin 10% (10 mg/kg) was administered every 24 h through intramuscular injection for 10 days, dipyrone/metamizole (25 mg/kg) every 24 h orally (PO) for 3 days, 0.5 ml (mL) of thymomodulin every 24 h PO for 30 days, and each 48 h for another 15 days. The lesions were cleaned and debrided every 15 days. Seventy-five days after the beginning of the treatment, the cutaneous lesions regressed, the animal gained weight, and was clinically stable. After treatment, the skin biopsy showed only mild epidermal acanthosis, intra-cellular edema, and mild lymphoplasmacytic perivascular dermatitis. No viral particles were observed by TEM and no poxviral DNA was amplified by PCR. This study documents the first case of confirmed and treated BPoPV infection in a hairy dwarf porcupine. The implemented therapeutic plan eliminated the infection and improved the general state of the animal., (© 2022. The Author(s) under exclusive licence to Sociedade Brasileira de Microbiologia.)