Background: Tumor necrosis factor alpha (TNFa) and its receptor (TNFa-R) play an important role in tumor genesis. However, their involvement in the recurrence of sarcomas is poorly studied. The purpose of this study was to analyze levels of TNFa and TNFa-R in the blood of patients with recurrent soft tissue sarcomas. Methods: The study included 64 male and female patients, mean age 63.4±5.2 years. Main groups included patients with recurrent G1 and G3 soft tissue sarcomas T2bN0M0; comparison groups included patients with primary G1 and G3 soft tissue sarcomas T2bN0M0. 95% of tumors were liposarcomas, with solitary rhabdamyosarcomas, myxofibrosarcomas, epithelioid and undifferentiated sarcomas. All recurrent patients had previously underwent surgical and radiation treatment for primary sarcomas and their relapses (up to 2 episodes), with the last surgery more than 1 year ago. Control groups (n = 10 each) included healthy donors of similar age. Levels of TNFa and TNFa-R were measured in the blood serum by ELISA before the treatment. Results: No significant differences were found between TNFa levels in patients with primary and recurrent soft tissue sarcomas and in donors. Levels of TNFa-R in men with primary G3 sarcomas were 1.5 times (p < 0.05) higher compared with donors, 1.7 times (p < 0.05) higher than in men with primary G1 sarcomas, and 1.3 times (p < 0.05) higher than in women with primary G3 sarcomas. TNFa-R increased by 1.7 times (p < 0.05) in all men with recurrent sarcomas regardless of the tumor grade, compared with the levels in healthy men; however, in G1 it was 1.9 times (p < 0.05) higher than in men with primary G1 sarcomas, while in G3 it did not differ significantly from the levels in men with primary G3 sarcomas. TNFa-R in women increased only in recurrent G3 sarcomas by 2.5 times compared to healthy women. No differences were observed in TNFa-R levels between men and women with recurrent G3 sarcomas. Conclusions: An excess of TNFa-R in the blood is characteristic for the recurrent soft tissue sarcomas G1 in older men and G3 in older women. At the same time, high grade tumors in men are accompanied by an increase in TNFa-R in the blood in both primary and recurrent sarcomas.