The aim of the study was to evaluate tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), soluble intracellular adhesion molecules 1 (s-ICAM-1) and Epstein–Barr virus (EBV) DNA load levels as predictors of hepatological complications of EBV infection in children. The study group consisted of 54 children aged one to eighteen years, who were hospitalised from 1 December 2018 to 31 December 2020 in the Department of Paediatrics, Infectious Diseases and Hepatology and who had hepatological complications in the course of serologically and molecularly confirmed EBV infection. It was shown that IL-6, TNF-α, and s-ICAM-1 concentrations were the highest in patients with hepatitis and biliary pole damage. Higher EBV DNA viremia positively correlated with increased C-reactive protein (CRP) and TNF-α levels and increased leukocyte, lymphocyte, and monocyte counts. Increases in lymphocyte counts and TNF-α concentrations were observed along with increases in gamma-glutamyl transpeptidase (GGTP) activity. Increased concentrations of IL-6, TNF-α, and s-ICAM-1 may indicate the risk of hepatitis with concomitant biliary pole damage during EBV infection.