Aims: Optimal outcome after cardiogenic shock (CS) depends on a coordinated healing response in which both debris removal and extracellular matrix tissue repair play a crucial role. Excessive inflammation can perpetuate a vicious circle, positioning leucocytes as central protagonists and potential therapeutic targets. High levels of circulating Triggering Receptor Expressed on Myeloid cells-1 (TREM-1), were associated with death in acute myocardial infarction confirming excessive inflammation as determinant of bad outcome. The present study aims to describe the association of soluble TREM-1 with 90-day mortality and with various organ injuries in patients with CS. Methods and results: This is a post-hoc study of CardShock, a prospective, multicenter study assessing the clinical presentation and management in patients with CS. At the time of this study, 87 patients had available plasma samples at either baseline, and/or 48 h and/or 96–120 h for soluble TREM-1 (sTREM-1) measurements. Plasma concentration of sTREM-1 was higher in 90-day non-survivors than survivors at baseline [median: 1392 IQR: (724–2128) vs. 621 (525–1233) pg/mL, p = 0.008), 48 h (p = 0.019) and 96–120 h (p = 0.029). The highest tertile of sTREM-1 at baseline (threshold: 1347 pg/mL) was associated with 90-day mortality with an unadjusted HR 3.08 CI 95% (1.48–6.42). sTREM-1 at baseline was not associated to hemodynamic parameters (heart rate, blood pressure, use of vasopressors or inotropes) but rather with organ injury markers: renal (estimated glomerular filtration rate, p = 0.0002), endothelial (bio-adrenomedullin, p = 0.018), myocardial (Suppression of Tumourigenicity 2, p = 0.002) or hepatic (bilirubin, p = 0.008). Conclusion: In CS patients TREM-1 pathway is highly activated and gives an early prediction of vital organ injuries and outcome. Graphic abstract: [Figure not available: see fulltext.].