Different devices for mechanical circulatory support (MCS) have been developed for the treatment of refractory cardiogenic shock. However, all of them are associated with direct blood contact, the need for anticoagulation and bleeding complications. To overcome these limitations the pericardial sac got into the focus as a promising implantation site for MCS. For this purpose, further knowledge about the mechanical properties of human pericardium is required. In this prospective, monocentric, experimental pilot study 56 samples of human pericardium were extracted postmortem from 13 critically ill patients. After preparation of test specimens uniaxial tensile tests were performed. The primary end points were load at fracture per sample width and strain at fracture. Acute inflammation was assessed by blood levels of C-reactive protein, white blood count and procalcitonin measured at several times during hospital stay. Inflammatory load was estimated by area under the inflammatory curves. Correlation and regression analysis were used to assess the relationship of primary end points to inflammation, comorbidities and postmortem time to preparation. Human pericardium showed a load at fracture per sample width of 1.95 [1.38–2.94] N/mm (median [inter quartile range]) and a strain at fracture of 89.29 [73.84–135.23] %. Markers of acute inflammation and cardiac hypertrophy did not correlate to load or strain at fracture. However, strain at fracture increased with higher body mass index and an increasing number of postmortem days. In contrast, higher patient age was associated with a lower strain at fracture. Inflammation and cardiac hypertrophy did not influence mechanical properties of human pericardium.