Background: The inflammatory response after trauma includes tumour necrosis factor alpha (TNF alpha) as pro-inflammatory cytokine. Furthermore, both soluble TNF receptor proteins (sTNF-R1 and sTNF-R2) were described to influence the post-traumatic inflammatory response and organ dysfunction. Method: From 47 trauma patients, blood samples were obtained at the scene of accident, at hospital admission, after 4 h, 12 h, and 24 h, and daily until day 6. Plasma levels of TNF alpha, sTNF-R1 and sTNF-R2 were measured by enzyme immunoassay (EIA) and analysed comparing clinical parameters such as injury scores (ISS, AIS), development of multiple organ dysfunction syndrome (MODS) and/or systemic inflammatory response syndrome (SIRS), and outcome. Results: Significant changes were observed in a time-dependent manner: TNF alpha and soluble TNF receptor levels were elevated compared to values of healthy persons. At 4 h after trauma, TNF alpha and sTNF-R2 showed an increase from initial values, which continued during the entire observation period. Severe trauma led to enhanced sTNF-R1 levels on scene and on hospital admission. Development of SIRS along with elevated sTNFR1 began on scene and was present on admission, with increased sTNF-R2 from day 1 to day 4. MODS (until day 6) was preceded by increased sTNF-R2 levels on admission and up to 4 h after trauma. Outcome was associated neither with TNF alpha nor with soluble TNF receptor levels. Conclusion: Thus, in trauma patients, early post-traumatic MODS and SIRS coincide with increased levels of TNF alpha and TNF receptor proteins, revealing different, time-dependent changes. Hence, detection of TNF alpha and soluble TNF receptor proteins after trauma should pay regard to the time point of sampling.