This study was performed to determine the risk factors associated with systemic complications of maxillofacial space infection (MSI), and to propose an objective evaluation index - severity score of MSI. 457 MSI patients from Jan 2010 to Dec 2020 were reviewed retrospectively. The predictor variables included demographic, origin of infection, underlying systemic disease, pre-hospital medication history, laboratory examinations and severity scores of space infection. The severity score of space infection was proposed to evaluate the airway compromise of anatomic spaces. The primary outcome variable was the complication. The impact factors of complications were analyzed using univariate analysis and multivariate logistic regression. 457 patients were included (average age 46.3 y, male to female ratio 1.43:1). Among them, 39 patients developed postoperative complications. In the complication group, there were 18 patients (46.2%) with pulmonary infection, and two patients died. We found that the history of diabetes mellitus (OR=4.74, 95% confidence interval (CI)=2.22, 10.12), high temperature (≥39°C) (OR=4.16, 95% CI=1.43, 12.06), advanced age (≥65 y) (OR=2.88, 95% CI=1.37, 6.01), and severity score of space infection (OR=1.14, 95% CI=1.04, 1.25) were independent risk factors for complications of MSI. All the risk factors needed to be closely monitored. Severity score of MSI was an objective evaluation index to predict complications.