Cardiac index (CI) and mean arterial pressure (MAP) are two key determinants of circulation, influencing global and regional blood flow. However, it remains unclear which of these parameters holds the leading role in the regulation of blood supply to organs in critical illness. The aim of our study was to assess the cumulative effects of hypotension, low CI and their combination on metabolic state and clinical outcome in sepsis and acute respiratory distress syndrome (ARDS). Material and methods. We performed a retrospective analysis of five prospective multiple-stage studies with parallel registration of invasive MAP, thermodilution CI, and 28-day survival. We estimated an incidence of low MAP (<65 mmHg), low CI (<2.5 L/min/m2) and distribution of four hemodynamic pairs (low MAP–low CI: MAPL—CIL; low MAP-normal or high CI: MAPL — CINH; normal or high MAP-low CI: MAPNH — CIL; normal or high MAP-normal or high CI: MAPNH — CINH) depending on clinical outcome. In addition, we assessed plasma lactate concentration, central venous oxygen saturation (ScvO2) and incidence of lactic acidosis in the hemodynamic groups. Data are presented as median (25th—75th percentile) or percentage. We analyzed data using Kruskal—Wallis test followed by U-test Mann—Whitney or using chi-square test. For all tests, p<0.05 was regarded significant. Results. Totally, we received 730 pairs of data from 106 patients with sepsis and ARDS. Low MAP was found in 14.7% of any stage in non-survivors and in 5.9% of any stages in survivors (p<0.01). Low CI was revealed in 13.7% of any stages in non-survivors and in 4.7% of any stages in survivors (p<0.01). Despite these similar results, the incidence of non-optimal hemodynamics (MAP–CI pairs with low MAP or low CI or both) was 10% in survivors and 25% in non-survivors (p<0.01). Moreover, lactate level and incidence of lactic acidosis were 10 (8–13) mmol/L and 86% in MAPL — CIL subset, 3 (2—8) mmol/L and 52% in MAPL — CINH subset, 3 (2—7) mmol/L and 43% in MAPNH — CIL subset and 2 (1—3) mmol/L and 27% in MAPNH–CINH subset (p<0.01 for MAPNH — CINH vs. all other groups). Lower values of ScvO2 were detected in hemodynamic pairs with low CI. In spite of the general tendency to metabolic worsening with deterioration of hemodynamics, in the same hemodynamic groups we found more significant metabolic shifts in deceased patients. Conclusions. The combination of mean arterial pressure >65 mm Hg and cardiac index >2.5 L/min/m2 in sepsis and ARDS provides optimal metabolic state and better clinical outcome. Prolonged cumulative unstable hemodynamics (hypotension or low cardiac index or both) is associated with worse clinical outcome.