During microcirculatory failure in septic shock, the relationship between modifications in macro-circulation and micro-circulation may depend on the resuscitation. How is the microcirculation modified during cardiac output (CO) increase by fluid? Four septic shock patients (73 ± 12 years old) were investigated with orthogonal polarization spectral imaging (OPS) and with a Swan–Ganz catheter. The SAPS score was 60 ± 8, and norepinephrine was 0.6 ± 0.3 μg/kg/min. In three sublingual areas per patient, the number of vessels (small, medium, large) were quoted as no flow = 0, sludge = 1, moderate = 2, normal = 3, allowing one to compute a microcirculatory ratio for each vessel category. Systemic hemodynamic and OPS data were taken before and within 30 min after fluid bolus (5–7 ml/kg). OPS data presented as median (interquartile range), demographic and hemodynamic data presented as median ± SE. Only the number of small vessels/field tended to increase after fluid from 34 (15) to 55 (21) (P = 0.09). In Fig. Fig.1,1, all vessel categories increased the ratio (P < 0.01). The blood pressure did not increase after fluid challenge, whereas the CO increased by 39 ± 18% (P < 0.05; Fig. Fig.22). Figure 1 Figure 2 SAP, systolic arterial pressure; DAP, diastolic arterial pressure; CVP, central venous pressure. All sizes of microvessels changed with fluid loading, with different patterns between small and larger vessels, going from recruitment to increased blood velocity.