The aim of this study was to evaluate the incidence of a variety of infectious complications in patients with CLL regarding the duration of CLL and the type of treatment. We present the retrospective analysis of patients with CLL treated at our institution in years 2004-2016. We collected data about the type of infection, pathogenes, treatment and severity of infections surpassed in connection with administration treatment. In the study one hundred and ten patients were evaluated. The average age of patients was 61.7 years (range 34.5-91.9 years). Fludarabine was the most widely used regimen, followed by bendamustine and alemtuzumab. We recorded 393 episodes of infections, of which 114 (29%) were severe and life threatening of degree 3-5, and 279 (71%) of degree 2. The most common infections were the upper respiratory tract infections together with sinusitis (45.03%), pneumonia (26.20%), CMV reactivation occured in 8.14%, infections of the skin was in 7.6 %. Most infections have occurred with the administration of monoclonal antibody alemtuzumab, these patients were at significantly higher risk of infection [RR 2.59 (1.30 to 5.17)] than patients receiving obinutuzumab [RR 0.63 (0.48 to 0.82)] (p = 0.0001). On the contrary, the safety profile of BCR signaling pathway inhibitors was very acceptable [RR 1.17 (0.70 - 1.96)]. The number of infections have decreased during the first 12 months of treatment with ibrutinib. In the study group we recorded 19 deaths, 8 (7.27%) of them were of infectious etiology. The risk of infectious complications is lifelong in patients with CLL, it can be minimized by early detection and aggressive management. Novel targeted agents used in therapy of CLL have a good safety profile, even the risk of infection is decreased during administration.