Background: Cardiogenic shock (CS) is characterized by impaired cardiac function, very high mortality, and limited treatment options. The pro-inflammatory signalling during different phases of CS is incompletely understood. Methods: We collected serum and plasma (N=44) as well as freshly isolated peripheral blood mononuclear cells (PBMC, N=7) of patients with CS complicating acute myocardial infarction on admission and after revascularization (24h, 48h, 72h) and of healthy controls (serum and plasma N=75; PBMC N=12). Results: PBMC of CS patients had increased gene expression of NLRP3, CASP1, PYCARD, IL1B, and IL18 and showed increased rates of pyroptosis (control: 4.7±0.3% vs. 9.9±1.7% in CS patients, p=0.02). Serum interleukin (IL)-1ß levels were increased after revascularization. IL-18 and IL-6 were higher in patients with CS than in healthy controls but comparable before and after revascularization. Pro-inflammatory apoptosis-associated speck-like proteins containing CARD (ASC) specks were elevated in the serum of CS patients on admission and increased after revascularization (admission: 11.1±4.4 specks/µl, after 24h: 19.0±3.9, p=0.02). ASC specks showed a significant association with 30-day mortality in patients with CS (p<0.05). The estimated regression coefficients and odds ratios indicated a positive relationship between ASC specks and mortality (Odds ratio 1.029, 95% CI, 1.000 to 1.072; p=0.02). Conclusions: Pyroptosis and circulating ASC specks are increased in patients with CS and are particularly induced after reperfusion This underscores their potential role as a biomarker for poor outcomes in CS patients. ASC specks represent promising new therapeutic targets for CS patients with high inflammatory burden.