【Objective】 To investigate the possible risk factors of sub-health neonates in Shandong province. 【Methods】 A population-based case-control study was carried out on 1 073 cases of sub-health neonates and 1 073 controls. The parents of cases and controls were interviewed with a uniformed questionnaire. The incidence was calculated and chi-square test was made to probe the statistical sense of exposure of risk factors using statistical software SPSS15.0. Conditional logistic regression model was used for multivariate analysis on SPSS. 【Results】 The chi-square test and multiple factor logistic regression analysis showed that some risk factors were mothers' age, fathers' smoking, mothers' passive smoking, raising pets, premature rupture of membrane, polyembryony, virus infection, pregnancy hypertension, taking nalgesics, tocolytic agent, morthers' exposure to noise, agricultural chemicals, and bad moral irritation, fathers' exposure to hor-mone drug. 【Conclusions】 The incidence of sub-health neonates is associated with many factors. Intended measures to prevent those risk factors could be effective in reducing the incidence of Sub-health Neonates.