INTRODUCTION Infections remain a major cause of morbidity and mortality in immunocompromised patients and require early diagnosis and treatment. However, correct diagnosis and treatment are often delayed by a multitude of factors. We report what we believe to be the first case of a combined disseminated infection with Nocardia and Mucor in a patient with systemic lupus erythematosus. CASE PRESENTATION A 74-year-old Caucasian woman with systemic lupus erythematosus presented with recurrent pneumonia. Despite empirical treatment with antibiotics, her condition gradually deteriorated. Microbiological sampling by thoracoscopy revealed the presence of Nocardia. Despite the institution of therapy for disseminated nocardiosis, she died of multi-organ failure. A post-mortem investigation confirmed nocardiosis, but showed concomitant disseminated mucormycosis infection as well. CONCLUSION Members of the bacterial genus Nocardia and the fungal genus Mucor are ubiquitous in the environment, have the ability to spread to virtually any organ, and are remarkably resistant to appropriate therapy. Both pathogens can mimic other pathologies both on clinical and radiological investigations. Invasive sampling procedures are often needed to prove their presence. Establishing a timely, correct diagnosis and a specific treatment is essential for patient survival.