BackgroundTissue oxygen saturation (StO2) decrease could appear earlier than lactate alteration. However, the correlation between StO2and lactate clearance was unknown.MethodsThis was a prospective observational study. All consecutive patients with circulatory shock and lactate over 3 mmol/L were included. Based on the rule of nines, a BSA (body surface area) weighted StO2was calculated from four sites of StO2(masseter, deltoid, thenar and knee). The formulation was as follows: masseter StO2× 9% + (deltoid StO2+ thenar StO2) × (18% + 27%)/ 2 + knee StO2× 46%. Vital signs, blood lactate, arterial and central venous blood gas were measured simultaneously within 48 h of ICU admission. The predictive value of BSA-weighted StO2on 6-hour lactate clearance > 10% since StO2initially monitored was assessed.ResultsA total of 34 patients were included, of whom 19 (55.9%) had a lactate clearance higher than 10%. The mean SOFA score was lower in cLac ≥ 10% group compared with cLac < 10% group (11 ± 3 vs. 15 ± 4, p = 0.007). Other baseline characteristics were comparable between groups. Compared to non-clearance group, StO2in deltoid, thenar and knee were significantly higher in clearance group. The area under the receiver operating curves (AUROC) of BSA-weighted StO2for prediction of lactate clearance (0.92, 95% CI [Confidence Interval] 0.82-1.00) was significantly higher than StO2of masseter (0.65, 95% CI 0.45–0.84; p < 0.01), deltoid (0.77, 95% CI 0.60–0.94; p = 0.04), thenar (0.72, 95% CI 0.55–0.90; p = 0.01), and similar to knee (0.87, 0.73-1.00; p = 0.40), mean StO2(0.85, 0.73–0.98; p = 0.09). Additionally, BSA-weighted StO2model had continuous net reclassification improvement (NRI) over the knee StO2and mean StO2model (continuous NRI 48.1% and 90.2%, respectively). The AUROC of BSA-weighted StO2was 0.91(95% CI 0.75-1.0) adjusted by mean arterial pressure and norepinephrine dose.ConclusionsOur results suggested that BSA-weighted StO2was a strong predictor of 6-hour lactate clearance in patients with shock.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12871-023-02139-4.