Sarcomas are a rare but fatal tumor type that accounts for <1% of adult solid malignancies and ~15% of childhood malignancies. Although the use of immunotherapy is being actively investigated for other solid tumors, advances in immunotherapy for sarcoma patients are lacking. To better understand the systemic immune environment in sarcoma patients, we performed a detailed multiplex analysis of serum cytokines, chemokines, and protumorigenic factors from treatment-naive subjects with localized, high-grade sarcoma. Because obesity is a major healthcare issue in the United States, we additionally examined the effects of obesity on serum protein profiles in our sarcoma subject cohort. We found that the systemic host environment is profoundly altered to favor tumor progression, with epidermal growth factor, angiopoietin-2, vascular endothelial growth factor A, IL-6, IL-8, and MIP-1β all increased relative to tumor-free controls (all p < 0.05). Surprisingly, we found that obesity did not exacerbate this protumorigenic profile, as epidermal growth factor and IL-8 decreased with increasing subject body mass index (both p < 0.05 versus normal or overweight subjects). The Th2-related cytokines IL-4, IL-5, and IL-13 were also decreased in the presence of obesity. Thus, although the systemic environment in sarcoma subjects favors tumor progression, obesity does not further aggravate the production of protumorigenic factors.