In the clinical setting, the role of systemic inflammation in patients with asthma has attracted increased attention, and some authors showed that increased IL-6 and high-sensitivity C-reactive protein characterized a group of asthmatic patients. In the realm of forensic pathology, a postmortem diagnosis of asthmatic death can be extremely challenging. The aim of this study was to determine the postmortem serum levels of C-reactive protein, IL-6, and tumor necrosis factor α in a series of severe acute bronchial asthma deaths that underwent medicolegal investigations. A total of 35 autopsy cases were retrospectively selected and included deaths in asthmatic subjects (related and unrelated to severe acute bronchial asthma, in situations characterized or not by systemic inflammation) as well as deaths in nonasthmatic individuals (in situations characterized or not by systemic inflammation). Our findings suggest that IL-6 is selectively increased in the systemic circulation of individuals with asthma, irrespective of whether the cause of death depends on a fatal asthma attack, compared with other biomarkers. Accordingly, postmortem serum IL-6 values in cases of death during severe acute bronchial asthma can be measured and considered of diagnostic relevance to estimate the magnitude of the systemic inflammation responses characterizing the disease.