Necrotizing soft tissue infection (NSTI) is a severe surgical infection which can result in sepsis and septic shock when generalized. The aim of the study was to determine the frequency of thrombocytopenia in patients with generalized NSTI, the factors promoting its development, and its association with septic shock. Materials and Methods. We examined 129 patients with NSTI treated between 09.2015 and 12.2019 at St. George Hospital in St. Petersburg, Russia. Surgical treatment, hematological and biochemical examinations, and bacteriological analysis of blood and wound discharge were performed in each patient. The studied group included 22 patients with systemic inflammatory reaction syndrome, 63 patients with sepsis, and 44 patients with septic shock. Results. We found a decrease in platelet count in NSTI patients with septic shock as early as on the first day of the disease and its further decrease within the next 3 days, with the mean platelet volume (MPV) increasing during the same period and significantly exceeding that in patients with sepsis and systemic inflammatory response syndrome. In NSTI patients with thrombocytopenia on admission, we found a significant correlation between the platelet count and the percentage of segmented neutrophils (r=0.349; P<0.001; n=40). The maximum incidence of septic shock was observed in patients infected with Klebsiella pneumoniae (13 out of 19, 65%). These patients had the highest MPV but did not develop thrombocytopenia. Maximum frequency of thrombocytopenia and elevation of MPV and platelet distribution width (PDW) was found in patients with NSTI and underlying chronic viral hepatitis C. However, the relative frequency of septic shock in these patients was not increased. Conclusion. The development of septic shock in NSTI is associated with a specific platelet activation pattern.