Brain and skull injuries in patients with polytrauma lead mostly to adverse outcomes. We investigated how such injuries influenced the physiology, infectious complications and outcomes. A total of 1465 patients with polytrauma were included in this retrospective cohort study with an Injury Severity Score (ISS) ≥ 16 and an age ≥ 16 years. The patients were subdivided into six groups according to the Abbreviated Injury Score (AIS) of the head. Marshall, Goris, Sequential Organ Failure Assessment (SOFA), Murray and Systemic Inflammatory Response Syndrome (SIRS) scores were calculated retrospectively. Infections were determined according to clinical signs and bacteremia. Data were analyzed using SPSS® 22.0; analysis of variance was used for continuous normally distributed data, the Kruskal–Wallis test was used for categorical data, and P < 0.05 was considered significant. The Marshall score increased along with the head AIS (P < 0.01). The Goris (P < 0.01) and SOFA (P < 0.01) score also increased significantly with increased head AIS. In the severe AIS groups the incidence of pneumonia was high (60%; P = 0.003) without correlation with the AIS of the thorax. Ventilator-assisted days increased significantly (P < 0.01) as well as the death rate (P < 0.01) along with the head AIS severity. The mortality reached 80% in the group with the maximum head AIS. These injuries have an adverse impact on physiology and outcome in polytrauma patients without being associated with the overall injury pattern. However, there appeared to be side effects of intensive-care-unit therapy on the patients’ physiology.