Cardiogenic shock (CS) is associated with high short-term mortality and a precise CS risk stratification could guide interventions to improve patient outcome. We used mass spectrometry based proteomics to first to a discovery approach to select some biomarker canduidates and then verify them by targeted mass spectrometry (PRM). A 4-protein risk score (CS4P) was derived and validated for 90-day risk of mortality. The CS4P risk score which comprises proteins Liver-fatty acid-binding protein (L-FABP), Beta-2-microglobulin (B2MG), Fructose-bisphosphate aldolase B (ALDOB), and SerpinG1 (IC1), identified short-term mortality risk with a C-statistic of 0.83 (95% CI 0.74–0.89).