OBJECTIVE Opportunistic infections in chronic lymphocytic leukemia (CLL) have been described in clinical trials, single-center studies, and case reports. We performed a nationwide study to estimate the incidence and impact of inpatient opportunistic infections. METHODS The incidence rate (IR) and incidence rate ratio (IRR) for Swedish CLL patients diagnosed 1994-2013, and matched controls were calculated, as well as the case-fatality ratio (CFR). RESULTS Among 8989 CLL patients, a total of 829 opportunistic infections were registered (IR 16.6 per 1000 person-years) compared with 252 opportunistic infections in 34 283 matched controls (IR 0.99). The highest incidence in the CLL cohort was for Pneumocystis pneumonia (200 infections, IR 4.03); Herpes zoster (146 infections, IR 2.94), and Pseudomonas (83 infections, IR 1.66) infections. The highest risk relative to matched controls was observed for Pneumocystis pneumonia (IRR 114, 95% confidence interval 58.7-252). The 60-day CFR for CLL patients with opportunistic infections was 23% (188/821), highest for progressive multifocal encephalopathy (5/7, 71%) and aspergillosis (25/60, 42%). CONCLUSIONS We have uniquely depicted the incidence of rare and serious infections in CLL patients and found a relatively high incidence of Pneumocystis pneumonia. Of the most common opportunistic infections, CLL patients with aspergillosis had the poorest prognosis.