Lay summary – Inflammation after severe traumatic brain injury can worsen recovery, but the immune processes involved are not fully understood. This study looked at blood samples from TBI patients over time and found that several proteins from the complement system, part of the body’s early immune response, were different from healthy people. One protein, C5, was linked to poorer recovery six months after injury. These findings suggest that the complement system may help predict outcomes and could be a future target for treatments after TBI.