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Lung infections with opportunistic pathogens, such as Pneumocystis or Nocardia, are infrequent in patients with severe asthma despite the use of high doses of inhaled or oral corticosteroids. We report two patients with severe eosinophilic asthma complicated by Nocardia infection in the respiratory tract. Both patients had exposure to chronic corticosteroid therapy and developed recurrent respiratory infections. The first patient had nodular pulmonary nocardiosis associated with hypocomplementemia and heterozygous variants in C1QB and NOD2, while the second patient had Nocardia farcinica tracheobronchitis, associated with selective immunoglobulin M reduction, and a heterozygous F508del mutation in the CFTR gene. Following appropriate antibiotic therapy and immunoglobulin replacement, both patients experienced fewer respiratory infections and stable pulmonary function. These cases highlight that opportunistic infections like Nocardia can occur in severe asthma under chronic immunosuppression, emphasizing the need for thorough immunologic evaluation and vigilant infection monitoring.