Objective. To determine the relationship between the level of soluble CD40 and CD40L (sCD40, sCD40L) and key characteristics of the course of multiple sclerosis. Material and methods. A comparative cross-sectional study covered 80 patients with multiple sclerosis diagnosed according to 2005 McDonald criteria. Enzyme immunoassay method was applied to measure the concentration of sCD40 and sCD40L in venous blood serum. Results. No significant changes in sCDL or sСD levels were found during acute MS periods in comparison to remission periods. The positive correlation between the frequency of exacerbations and the level of sCDL was shown. Conclusion. No evidence for the association between indexes of activity of the sCD40-sCD40L system in blood and both exacerbation of MS, severity and rate of neurological impairment in this disease was demonstrated.