Background: Guatemala is a country with the highest prevalence of stunting in under-5 children in the Americas, with a national average of 49.8%. Asymptomatic intestinal colonization with Giardia intestinalis is common in Guatemalan preschoolers and has been implicated as a factor in linear growth retardation. The potential mechanisms of any giardiasis-growth interaction have not been exhaustively explored. Objectives: The aim of the present study was to describe urine oxidative stress biomarkers and erythrocyte antioxidant enzyme activity, and to explore any association with prevalence or intensity of G intestinalis infection in preschoolers attending 3 government-subsidized day care centers in the Guatemalan Western Highlands. Methods: Samples of feces, urine, and red blood cell (RBC) hemolysate were collected in a total of 74 preschoolers enrolled in 3 day care centers. Giardia prevalence and a proxy index for intensity were assessed by enzyme-linked immunosorbent assay (ELISA). Urinary biomarkers of oxidative damage to DNA (8-hydroxydeoxyguanosine [8-OHdG]) and to lipid (F2t 15-Isoprostane [F2-Iso]) were measured by ELISA. The erythrocyte activity of catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GSR), and glutathione peroxidase (GPX) were measured by respective spectroscopic substrate-based reaction assays. Results: Median values of RBC CAT activity (P = 0.016) and urine F2-Iso (P = 0.023) differed between children who were positive (n = 39) and negative (n = 35) for Giardia. Similarly, G intestinalis intensity was significantly and positively associated with urinary F2-Iso (r = 0.446, P < 0.001), RBC SOD (r = 283, P = 0.014), and RBC CAT (r = 0.260, P = 0.025). Conclusion: The optical density reading of the fecal ELISA assay for G intestinalis has potential as a proxy for the intensity of infestation. In this respect, there exists an association of this intensity with indicators of the systemic oxidation.