Despite numerous investigations, fatigue remains one of the least studied manifestations of MS. However, significant prevalence of this symptom proves importance of its study. The aim of the study was to define a prognostic assessment of fatigue development accompanying lesions of certain functional systems and degree of disability. Material and methods. 96 patients, aged 15 to 58 years with a diagnosis of MS have been examined. MS patients were examined with the same protocol, using formalized scales. To detect fatigue and determine the degree of its severity was used Fatigue Severity Scale (FSS). The degree of disability in patients was assessed by Kurtzke EDSS (Expanded Disability Status Scale). Statistical methods for the data analysis were also used, including methods of descriptive statistics, probability assessment and prognostic significance of obtained data using odds ratio (OR). Results. Fatigue was detected in 49.1% of patients with a degree of disability lower than 4 EDSS scores and in 90.4% of patients with disability higher than 4 EDSS scores (p=0.0027). The assessment of functional systems at the time of observation has statistically significant prognostic values according to the following parameters: pyramidal system lesion (OR=7.43 (2.43–22.76)), coordination disorders (OR=4.60 (1.05–20.25)), cranial nerve lesion (OR=4.33 (1.40–13.39)), (p<0.05). Lesion of the pyramidal and coordination systems at the onset of the disease may increase risk for detection of fatigue higher than 4 scores in the follow-up observation (lesion of pyramidal system – OR=1.62 (0.5–5.25), coordination disorders OR=1.41 (0.58–5.16)). Conclusion. The results of our investigation showed that symptom of fatigue is observed in almost 90 % of MS patients. The study showed that fatigue in MS patients depends on the degree of disability and lesions of certain functional systems.