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Background: Episodic fever syndromes are commonly seen in pediatric practice. Episodic fever of unknown origin (FUO) lasts for a few days or weeks and is followed by a fever-free period with a sense of well-being. In this condition, activated neutrophils and monocytes intensively generate reactive oxidative species that may further damage various molecules. The aim of the study was to evaluate oxidative stress biomarkers, lipid peroxidation in erythrocytes and plasma, and advanced oxidation protein products (AOPP) in children with episodic FUO. Methods: The study enrolled 25 children with episodic FUO in afebrile phase and 25 healthy children as controls. Lipid peroxidation was evaluated by measuring malondialdehyde (MDA) production with the thiobarbituric-acid-reactive substances (TBARS) assay in erythrocytes and plasma. Oxidative modification of proteins was measured spectrophotometrically by the determination of AOPP in plasma. Results: Mean duration of episodic fevers was 3.96±2.8 years. Erythrocyte MDA levels were higher in children with FUO than in controls (86.26±10.75 vs. 78.0±3.21 nmol/g hemoglobin), although not significantly (p=0.202). The MDA plasma concentrations were similar (2.42±0.35 vs. 2.41±0.39 μmol/L) between the groups (p= 0.732). Unexpectedly, levels of AOPP were significantly lower in children with FUO than in healthy controls (18.8±5.04 vs. 25.1±3.35 μmol/L, p=0.047). Conclusions: Episodic fevers of unknown origin with an average duration of 3.96±2.8 years do not cause significant oxidative modifications of lipids and proteins in children.