Background: The Burkholderia cepacia complex (Bcc) is an opportunistic pathogen in humans and animals. Deep pyoderma caused by these bacteria in dogs has been previously reported. This case series aims to describe contrasting treatment responses in Bcc-related deep pyoderma in two dogs, a male and a female. Case Description: Both patients had a history of immune-mediated polyarthritis (IMPA) managed with oral ciclosporin and prednisolone. Their skin lesions were multifocal, irregular, erythematous to hemorrhagic, alopecic papules, plaques, and nodules, with extensive crusting, draining tracts, and ulceration. Cytological findings revealed a marked inflammatory response consisting of non-degenerative and degenerative neutrophils and macrophages, with moderate to abundant intracellular and extracellular Bcc. Ciclosporin and prednisolone were stopped in case 2 after diagnosis. However, it was challenging to stop the regimen in case 1 because of the recurrence of IMPA and the onset of iatrogenic hypoadrenocorticism. Case 1 did not achieve remission for approximately 66 weeks even with seven protocols because of multiple relapses, whereas it took only 3 weeks to achieve remission in case 2 while using one drug. Conclusion: For deep pyoderma with extensive lesions in immunosuppressed patients, one should consider infection with Bcc. Therefore, immunosuppressants should promptly be reduced in such patients, and then, intensive antimicrobial therapy may achieve remission.