Abstract Purpose Optimal management of retroperitoneal soft tissue sarcoma (RPS) often requires extensive tumor resections, frequently involving gastrointestinal organs. The impact of these procedures on the nutritional status and hemoglobin (Hb) levels of RPS patients remain unexplored. In this study, we aimed to evaluate preoperative nutritional status as well as the prevalence of anemia in RPS patients, and to investigate longitudinal changes throughout the disease course in order to identify potential strategies for prehabilitation. Materials and methods Patients undergoing resection of primary and recurrent RPS at Heidelberg University Hospital were retrospectively analyzed. Changes in nutritional parameters and Hb levels throughout the disease course were analyzed using hierarchical linear regression models. Multivariable Cox regression analyses were performed to identify independent predictors of overall survival. Subgroup analyses were conducted for primary tumors, first, second and third recurrences. Results Amongst 370 patients analyzed, comprising 219 with primary disease, we observed neither a significant prevalence of preoperative malnutrition nor notable changes in BMI or serum albumin levels throughout the disease course. Preoperative anemia affected up to 40% of RPS patients, and Hb levels significantly decreased over the course of the disease (p = 0.022), particularly in correlation with the number of tumor resections performed (p = 0.010). Low preoperative Hb levels were associated with increased 30-day mortality and they were identified as an independent prognostic factor for shorter overall survival in primary RPS as well as in second and third recurrences. Conclusion Anemia screening should be performed preoperatively and during regular follow-ups to enable early-on therapy, thus potentially improving patient outcomes in RPS.