OBJECTIVE To assess whether non-surgical periodontal treatment is associated with changes in serological markers of systemic inflammation. METHODS Thirty-five systemically healthy subjects with severe generalized periodontitis meeting the inclusion criteria participated in a four-month single blind interventional trial of which thirty-two completed the study. Periodontal parameters and inflammatory markers [C-reactive protein (CRP) and plasma fibrinogen] and also the white blood cell count (WBC) were evaluated prior to and four months after delivery of intensive non-surgical periodontal therapy with simultaneous lavage of chlorhexidine 0.1% from the tip of the ultrasonic instrument into the pockets. RESULTS Significant differences in serum CRP levels were observed four months after treatment compared to the baseline (1.85, SD=1.93 vs 2.46, SD=2.32, respectively, P<0.0001). Periodontal treatment also resulted in a significant difference in WBC and neutrophil counts compared to the baseline (P<0.0001). The reduction in fibrinogen levels was not significant at the end of the research period. Significant improvement in the pocket probing depth and clinical attachment level for pockets with initially 4-6 mm and then more than 7 mm depth was observed. Changes in plaque and bleeding scores were also statistically significant (82.75 vs. 35.84 and 19.03 vs. 1.81, respectively). CONCLUSIONS Periodontal treatment is effective in reducing CRP levels and white blood cell count, while fibrinogen levels are not influenced by periodontal therapy. Periodontal treatment may therefore decrease the systemic inflammatory burden in patients with advanced periodontitis.