- Background Opportunistic infections (OIs) can be defined as infections in immunosuppressed patients that are more frequent or severe because of immunosuppression. The literature on OIs in pemphigus is sparse. Objective We assessed the incidence, risk factors, and characteristics of OIs in patients with pemphigus. Methods This was a historical prospective study following a cohort of 172 patients with newly diagnosed pemphigus for the development of OIs. Results Fourteen patients developed OIs at a mean of 4 months from the time of diagnosis while taking a mean dose of 0.8 mg/kg/day of prednisone, 5 in conjunction with azathioprine. The risk of developing an OI in the first year after the diagnosis of pemphigus was 9.3%, subsequently dropping to 0. Advanced age and possibly diabetes were found to be risk factors for OI development. Infectious agents included Nocardia, cytomegalovirus, Legionella, and Listeria. Two patients died within 2 months of OI diagnosis, and 2 more had neurologic impairment. Limitations Limitations include the extraction of historical data and the cohort originating from a single geographic region. Conclusion OIs present in a significant number of patients with pemphigus during the first year after the diagnosis of pemphigus, with potential deleterious effects. Older and possibly diabetic patients are at increased risk. Physician vigilance and patient education on limiting pathogen exposure is recommended.