INTRODUCTION: Pneumocystis jirovecci pneumonia (PJP) is an opportunistic fungal infection occurring in immunocompromised patients, such as those with human immunodeficiency virus (HIV), organ transplantation, malignancies and connective tissue diseases (CTDs). Risk factors for PJP are not well characterised, leading to uncertainty regarding the indications for antimicrobial prophylaxis and monitoring. This study compared differences between patients with and without CTDs who developed PJP. METHODS: Retrospective data was collected for all subjects with a positive toludine blue O stain or a positive P. jirovecci PCR and a concurrent respiratory illness that was clinically consistent with PJP between 2002 and 2013 at the Royal Melbourne Hospital, Australia. Sub-groups were assigned according to the underlying disease. Peripheral blood results were retrieved from an in-house pathology database. RESULTS: Eleven of 90 subjects (12.2%) diagnosed with PJP had underlying CTDs. The CTDs group was more likely to have been exposed to corticosteroids (100% versus 35.2%, p < 0.001) and other iatrogenic immunosuppression (90.9% versus 24.6%, p < 0.001). After adjusting for age and gender, the CTDs group had greater lymphopaenia (0.17 versus 0.58 × 10(9)/L; p = 0.034) and were older (69.6 versus 50.6 years; p < 0.001) than the non-CTD group. Excluding renal transplant recipients, people with CTDs also had lower eGFR than the non-CTD group (65 versus 80; p = 0.015). CONCLUSIONS: CTDs contributed to a significant proportion of total PJP diagnoses. Clinicians treating CTDs must be vigilant for PJP, particularly in older patients with exposure to corticosteroids or other iatrogenic immunosuppression, lymphopaenia and renal impairment; factors which may lower the clinical threshold for initiating prophylaxis. Copyright © 2015 Elsevier Inc. All rights reserved.