To explore the effect of naloxone in adjuvant treatment of septic shock and its influence on lactic acid clearance rate and sublingual microcirculation state. Methods A prospective study was conducted on 86 patients with septic shock admitted to our hospital from October 2019 to April 2021. According to the random number table method, they were divided into an observation group and a control group at a ratio of 1∶1, with 43 cases in each group. The control group received conventional treatment, and the observation group was treated with naloxone adjuvant therapy on the basis of the control group. The efficacy, lactic acid clearance rate, blood lactic acid, heart rate (HR), mean arterial pressure (MAP), central venous pressure (CVP) level, sublingual microcirculation state ［total blood vessel density (TVD), ratio of perfused blood vessels］ (PPV), perfusion vessel density (PVD), microvascular flow index (MFI)］, cerebral oxygen metabolism ［internal jugular venous blood oxygen saturation (SjvO2), cerebral oxygen saturation (rSO2), blood oxygen content difference (Da-jvO2), cerebral oxygen uptake rate (CEO2)］ before and after treatment and incidence of adverse reactions were compared between the two groups. Results The total effective rate of 93.02% in the observation group was higher than 76.74% in the control group (P＜0.05). After treatment, the blood lactic acid level of the observation group was lower than that of the control group, and the lactic acid clearance rate was higher than that of the control group (P＜0.05). After treatment, the levels of HR in the two groups were lower than before treatment, and the levels of MAP and CVP were higher than before treatment (P＜0.05), but there was no statistically significant difference between the groups (P＞0.05). After treatment, TVD, PPV, PVD, MFI, SjvO2, rSO2 in the observation group were higher than those in the control group, and Da-jvO2 and CEO2 were lower than those in the control group (P＜0.05). There was no statistically significant difference in the incidence of adverse reactions between the two groups (P＞0.05). Conclusion Naloxone has a significant effect in adjuvant treatment of septic shock patients. It can effectively reduce the level of lactic acid, increase the lactic acid clearance rate, improve the sublingual microcirculation state and cerebral oxygen metabolism, and has high safety