Key Clinical MessageImmunosuppression, malnutrition, and underlying infection can unmask obscure infections which can be challenging to identify. Early diagnosis and treatment of infections in immunosuppressed patients are essential due to high morbidity and mortality.AbstractThe immunosuppressive effects of treatment for ulcerative colitis (UC), including chronic corticosteroids, anti‐TNF agents, and JAK inhibitors, can impact the spread of latent or obscure infections. Clinicians should have a low threshold for pursuing aggressive diagnostic and therapeutic intervention in patients who show signs of clinical deterioration while on immunosuppressing medications. Our unique case highlights an immunosuppressed patient with UC who developed Nocardiosis after initiation of upadacitinib while hospitalized for concurrent UC flare andClostridium difficileinfection.