Secondary morbidity and mortality after trauma are mainly due to a dysfunctional immune system. Severe injury can trigger a systemic inflammatory response, which is characterised by pre-activation or priming of neutrophils in peripheral blood. Signals initiated as result of local tissue damage can further activate these neutrophils leading to post-injury inflammatory complications. Additional trauma caused by surgical intervention can worsen the inflammatory response, thereby increasing the risk of these inflammatory complications. Limiting surgical procedures through damage control principles can reduce the risk of secondary morbidity. Inflammatory complications after injury cannot adequately be predicted using the current anatomical and physiological-based scoring systems. In this review we propose a methodology focussing on the activation state of the systemic inflammatory response with focus on neutrophils to aid in the risk assessment of secondary morbidity after trauma. Neutrophils are essential effector cells during the post-injury systemic inflammatory response. Neutrophils differentially express an array of surface receptors by which the cells can respond and adapt to changing environmental signals. The determination of specific expression profiles of neutrophil receptors can aid in phenotyping and quantifying the systemic inflammatory response. This article reviews the application of these specific signatures of neutrophil receptors as a consequence of severe injury.