This prospective study investigated the levels of procalcitonin (PCT) and C-reactive protein (CRP) in patients with various types and severity of multiple trauma, and their relationship to trauma-related complications. Adult multiple-trauma patients (n = 113) admitted to the intensive care unit (ICU) in the first 24 h after trauma were included. The Injury Severity Scores (ISS), and PCT and CRP levels were measured in the first 24 h (day 1), on day 7 and on the final day of their ICU stay. Survival at 30 days was recorded. Mean PCT and CRP levels were both significantly higher on day 7 compared with day 1 and the final assessment day in patients with an ISS > 20. Levels of PCT were significantly higher in cases with sepsis, severe sepsis or septic shock compared with cases who developed systemic inflammatory response syndrome (SIRS), however levels of CRP were significantly higher only in cases with severe sepsis or septic shock, but not in cases with sepsis alone. These data support the view that PCT levels may be a better indicator than CRP levels in the early diagnosis of septic complications in patients with multiple trauma.