Objective. To investigate the correlation between serum immune factor levels and allergic constitution in children with infectious mononucleosis. Methods. A total of 120 children who visited our hospital from March, 2019, to December, 2020, were selected as the research objects, and 40 children who came to our hospital for physical examination were included in the control group (CG). 40 children with IM were classified into the IM group (IG), and 40 IM children with allergic rhinitis, allergic dermatitis, asthma, and other allergic diseases were classified into the IM allergy group (AG). On the second day of admission, 5 ml of fasting venous blood was collected from all children in the early morning to observe the serum IgE level, the level of lymphocyte subsets, and the level of immunoglobulin of the patient. Results. The serum CD3, CD4, and CD8 levels of children in AG were significantly higher than those in IG and CG (
P
<
0.05
). The serum IgE, IgA, IgM, and IgG levels of children in AG were significantly higher than those of IG and CG (
P
<
0.05
). The serum IgE levels of children in AG were positively correlated with the serum CD3, CD4, and CD8 levels (
P
<
0.05
). There was a positive correlation between the serum IgE level and serum IgA, IgM, and IgG levels in children with AG (
P
<
0.05
). Conclusion. The results of this study showed that there may be a certain relationship between allergic constitution and the incidence, clinical manifestations, and prognosis of infectious mononucleosis. IgE level can be used as a reference index for the early severity of IM clinical symptoms.