Background: Trauma is still a major cause of mortality in people Methods: Cell-free DNA (cfDNA) and further laboratory markers were determined in plasma and serum of 164 patients at time of admission to the emergency room. Among them were 64 patients with severe trauma (Injury Severity Score (ISS) ≥ 16), 51 patients with moderate trauma (ISS Results: cfDNA levels in plasma and serum were significantly higher in patients with severe multiple trauma (SMT) than in those with moderate trauma (p = 0.002, p = 0.003, respectively) or with single fractures (each p p 8). Thirteen (20.3%) of the multiple trauma patients died during the first week after trauma. Levels of cfDNA were significantly higher in non-surviving patients than in survivors (p Conclusions: cfDNA is valuable for estimation of trauma severity and prognosis of trauma patients.