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Objective: To explore the value of lactic acid (Lac), lactate clearance (LCR) and procalcitonin (PCT) in assessing the severity and predicting the prognosis in sepsis., Methods: 18-80-year-old patients with sepsis admitted to the department of critical care medicine of Beijing Friendship Hospital, Capital Medical University from April 2009 to December 2019 were enrolled. The gender, age, basic illness, infection site, organ function, acute physiology and chronic health evaluation II (APACHE II), sequential organ failure assessment (SOFA), Lac and PCT were collected on admission to intensive care unit (ICU), as well as Lac after 24 hours, 24-hour LCR, and 28-day prognosis. The patients were divided into sepsis group and septic shock group according to Sepsis-3 criteria. According to the 28-day prognosis, the septic shock patients were divided into survival group and death group, and the differences of each index between the two groups were compared. Multivariate Logistic regression was used to analyze the risk factors of death in septic shock patients. The receiver operating characteristic (ROC) curve was used to analyze the role of Lac, LCR, PCT, SOFA score and APACHE II score in predicting prognosis of the patients with septic shock., Results: A total of 998 patients with sepsis were enrolled, including 642 males and 356 females; with (59.56±13.22) years old. There were 478 patients with septic shock, among which 180 died and 298 survived during the 28-day observation. (1) Compared with the sepsis group, the age of the sepsis shock group was significantly higher (years old: 60.49±12.31 vs. 58.72±13.97), APACHE II score, SOFA score, Lac, PCT and 24 h Lac increased [APACHE II: 24.57±7.04 vs. 19.37±6.93, SOFA: 7.78±3.31 vs. 4.38±3.42, Lac (mmol/L): 3.00 (1.70, 5.00) vs. 1.40 (1.00, 2.30), PCT (μg/L): 0.05 (0.00, 4.00) vs. 0.00 (0.00, 1.10), 24-hour Lac (mmol/L): 2.60 (1.60, 4.40) vs. 1.40 (1.00, 2.20)], and the 28-day mortality was significantly higher [41.63% (199/478) vs. 19.42% (101/520)], with significant statistic differences (all P < 0.05). (2) Compared with the survival group, APACHE II score, SOFA score, Lac, 24-hour Lac significantly increased in the septic shock death group, and 24-hour LCR decreased [APACHE II: 26.19±6.52 vs. 22.25±6.07, SOFA: 9.07±2.90 vs. 7.50±3.10, Lac (mmol/L): 3.80 (2.50, 5.10) vs. 2.80 (2.00, 3.90), 24-hour Lac (mmol/L): 3.20 (2.20, 5.60) vs. 2.10 (1.60, 3.30), 24-hour LCR: 1.43 (-37.50, 30.77)% vs. 16.67 (0.00, 33.98)%, all P < 0.05]. In assessment of organ function, central venous pressure (CVP) and oxygenation index (PaO 2 /FiO 2 ) were lower in death group [CVP (mmHg; 1 mmHg = 0.133 kPa): 5.00 (2.00, 8.00) vs. 6.00 (2.00, 9.00), PaO 2 /FiO 2 (mmHg): 184.21±84.57 vs. 199.20±86.98], alanine aminotransferase (ALT) and serum creatinine (SCr) increased [ALT (U/L): 376.56±41.43 vs. 104.17±14.10, SCr (μmol/L): 213.53±8.06 vs. 181.91±5.03], with significant statistic differences (all P < 0.05). (3) Multivariate Logistic regression analysis showed that PaO 2 /FiO 2 , SCr, Lac and SOFA were independent risk factors of prognosis in septic shock [PaO 2 /FiO 2 : odds ratio (OR) = 0.997, 95% confidence interval (95%CI) was 0.996-0.999, P = 0.001; SCr: OR = 1.001, 95%CI was 1.000-1.002, P = 0.041; Lac: OR = 0.925, 95%CI was 0.871-0.982, P = 0.011; SOFA: OR = 1.178, 95%CI was 1.110-1.251, P = 0.000]. ROC curve analysis showed that SOFA, SOFA+APACHE II, Lac+24-hour LCR+PCT+SOFA+APACHE II could predict mortality in septic shock patients, and the area under the ROC curve (AUC) was 0.769 (95%CI was 0.740-0.798), 0.787 (95%CI was 0.759-0.815), 0.800 (95%CI was 0.773-0.827), respectively. The joint of the five indicators, Lac, 24-hour LCR, PCT, SOFA and APACHE II has the largest AUC., Conclusions: Lac is an independent risk factor for death in patients with septic shock, however, the prognosis cannot be predicted. Comprehensive analysis of LCR, PCT, SOFA, APACHE II and the clinical organ functions are required for analysis.