Severe burns induce a complex systemic inflammatory response characterized by a typical prolonged acute phase response (APR) that starts approximately 4–8 h after-burn and persists for months up to a year after the initial burn trauma. During this APR, acute phase proteins (APPs), including C-reactive protein (CRP) and complement (e.g. C3, C4 and C5) are released in the blood, resulting amongst others, in the recruitment and migration of inflammatory cells. Although the APR is necessary for proper wound healing, a prolonged APR can induce local tissue damage, hamper the healing process and cause negative systemic effects in several organs, including the heart, lungs, kidney and the central nervous system. In this review, we will discuss the role of the APR in burns with a specific focus on complement.