Three healthy pregnant women without obstructive sleep apnea (OSA) (C), three pregnant women with mild OSA (O), and three pregnant women with moderate (MO) OSA were enrolled to identify serum diagnostic biomarkers-associated with the severity of OSA during pregnancy. Differentially expressed proteins (DEPs) among control (C), mild (O), and moderate (MO) OSA groups were identified. Bioinformatics analysis was conducted to discover the underlying functions, pathways and networks of the proteins. Furthermore, receiver operating characteristic curve (ROC) curve was used to assess the diagnostic value of the identified DEPs. A total of 141, 29, and 103 DEPs were identified among the three groups. C1R and A2M were identified as continuously upregulated proteins, and the levels of C1R and A2M were related with the severity of OSA.