We report the case of a 50-year-old man with allergic bronchopulmonary mycosis (ABPM) complicated with bilateral septic arthritis of the knees caused by Methicillin-resistant Staphylococcus aureus (MRSA). He had a background of bronchial asthma and end-stage renal failure on maintenance dialysis. He was treated with 30 mg/day of prednisolone for 14 days for ABPM. He developed bilateral septic arthritis of the knees, caused by MRSA during prednisolone treatment. He underwent bilateral arthroscopic washout with a 2-week course of intra-articular arbekacin, concomitantly treated with a 6-week course of intravenous teicoplanin and oral rifampicin, subsequently followed by oral linezolid treatment. However, he suffered exacerbation of ABPM during treatment of septic arthritis. Because of these serious infectious complications, he was treated with mepolizumab instead of corticosteroids for the ABPM, which resolved all symptoms and clinical features. This case highlights mepolizumab treatment as an alternative to corticosteroid therapy for treatment of ABPM in patients with comorbidities such as infection.