Introduction: Infliximab is an effective therapy for induction and maintenance of remission in patients with refractory ulcerative colitis (UC). Treatment with TNF-alpha inhibitors is associated with an increased risk of infection. In this case, we will discuss an uncommon cause of infection associated with infliximab therapy despite antibiotic prophylaxis. Case description: 78-year-old man with history of UC maintained on infliximab infusion every 8-weeks was found to have pulmonary infiltrates on chest computed tomography (CT). His UC history was notable for recent Pneumocystis jiroveci pneumonia while on inflix- imab requiring intravenous Trimethoprim/Sulfamethoxazole (TMP/ SMX) treatment for 21 days followed by single strength oral TMP/SMX for secondary prophylaxis. On evaluation, the patient endorsed weakness, generalized fatigue, and shortness of breath with activities. His lab was notable for mild anemia in the absence of leukocytosis. Result and conclusion: Bronchoscopy was performed and bronch- oalveolar lavage fluid was sent to the microbiology laboratory for culture. After 30 days of incubation, the culture returned partially acid fast, branching, Gram-positive rod shaped bacteria consistent with Nocardia cyriacigeorgica. The isolate was susceptible to TMP/SMX (0.25/4.75μg/Ml). Patient was started on therapeutic dose of oral TMP/SMX at 5 mg/kg of the trimethoprim component for 6 months. Infliximab was subsequently held. Repeat chest CT scan at 6 months showed resolution of patchy ground glass and nodular infiltrates. Take-home message: This case highlights the importance of con- sidering Nocardia infection in ulcerative colitis patients receiving inflix- imab therapy presenting with shortness of breath and new infiltrates on chest imaging. In addition, patients receiving prophylaxis with TMP/SMX are still at risk for this infection because the effectiveness of prophylactic doses of TMP/SMX in preventing disease remains unclear.