Current scientific consensus about the physiopathology in the progression from severe sepsis to septic shock and death focuses on myocardial contractile dysfunction. Nevertheless, objective parameters to establish a pathological correlate of a fatal outcome are lacking; then a cause of death due to sepsis can remain an unsolved problem. We first reviewed all death cases recorded at our institutions during the period from 2007 until 2015. Then, we conducted a retrospective study of a selected autopsy series of people who had received "sepsis" as cause of death. Two pathologists re-examined the heart sections while the most suitable myocardial sample for each case was stained for immunohistochemistry with antibodies targeted for specific inflammatory-related molecules. We used specific antibodies for the following markers: alpha-smooth muscle actin (alpha-SMA); fibronectin; matrix metallopeptidase 9 (MMP-9); intercellular adhesion molecule 1 (ICAM-1); caspase-3; lactoferrin (LF); cluster differentiation 15 (CD15). The statistical significance of differences was assessed using student's t-test for unpaired data or non-parametric Mann-Whitney or Wilcoxon tests for skewed variables or one-way analysis of variance and post hoc Scheffe's test for continuous variables and Pearson's χ-test for discrete variables. Linear regression analysis was used to determine the presence of a correlation between continuous variables. At our institutions, 2220 deaths have been recorded during the period study. Sepsis accounted as a cause of death for the 20% of total. We finally enrolled 56 cases; of these, only 20 were positive for microbiological analysis. At histological examination, clear inflammation was detectable in the 32% of cases; otherwise, immunohistochemical reaction showed a positive reaction for LF and CD15 in more than a half cases (56%). We still ignore all the underlying mechanisms of sepsis and all its pathophysiological connections with cardiac metabolism; in this sense, we aim to corroborate the diagnostic value of anti-LF and anti-CD15 staining for the post-mortem detection of myocardial inflammation.