Epstein–Barr virus (EBV) infection is a common infectious disease in young adults and children. A 4‑year‑old boy was presented with enlarged tonsils and purulent discharge. Sudden airway collapse and desaturation were noted, and endotracheal tube intubation was performed. The laboratory data demonstrated positive results for EBV immunoglobulin M (IgM). Polyclonal B‑cell activation that led to positive results for cytomegalovirus (CMV) IgM and herpes simplex virus (HSV) IgM was also detected by the interference of heterophilic antibodies. A low‑dose intravenous immunoglobulin (IVIG) infusion was performed, and an IVIG‑related false‑positive result for CMV immunoglobulin G (IgG) was observed. After the aggressive medical care, the boy was discharged under a stable condition. Herein, we report the important features of EBV‑related infectious mononucleosis that harvested multiple interferences. First, the heterophilic antibodies caused due to polyclonal B‑cell activation resulted in the false‑positive result for CMV IgM and HSV IgM. Second, the IVIG interpreted the CMV IgG. We must be aware of the multiple interferences that could misinterpret our laboratory data.