Objective：To evaluate the differential diagnosis value of serum complement C3 in adult-onset Still’s disease（AOSD）and sepsis. Methods：A total of 58 patients with AOSD and 50 patients with sepsis were collected from the First Affiliated Hospital of Nanjing Medical University from 2016 to 2019，and 50 physical examinees were selected as health control. Serum complement C3 levels in the three groups were detected, and differences in other laboratory indicators were compared between AOSD patients and sepsis patients. Univariate and multivariate factors were used to analyze the relationship between each variable and the occurrence of AOSD. ROC curve was used to explore the diagnostic efficacy of complement C3 and serum ferritin levels in AOSD and sepsis. Results：C3 level in AOSD group（1.49±0.24）g/L is significantly higher than that in sepsis group（1.00±0.37）g/L，there were statistical significance in the high density lipoprotein cholesterol，ferritin，C3 between two groups. In multivariate analysis，ferritin≥472.20 ng/mL（OR=56.97，95%CI：2.22~1 463.44，P < 0.05），C3≥1.20 g/L（OR=27.80，95%CI：3.22~240.28，P < 0.01） and high density lipoprotein cholesterol≥0.82 mmol/L（OR=13.34，95%CI：1.01~176.29，P < 0.05） were independently related with AOSD. The area under the curve（AUC） of serum C3 in the differential diagnosis of AOSD and sepsis was 0.81（95% CI：0.63~1.00），and the diagnostic sensitivity and specificity were 0.90 and 0.73 when C3 critical value was 1.21，which reached the maximum diagnostic efficacy. However，when C3 combined with ferritin was used for differential diagnosis，the AUC was 0.86（95%CI：0.75~0.96）. Conclusion：Serum C3 can be used as a differential diagnostic index of AOSD and sepsis，and has clinical value in the diagnosis of AOSD.