The aim of this study was to trace an exposure profile to traffic-derived pollution during pediatric age. For this purpose, two biomonitoring campaigns for the determination of urinary (u-) methyl tert-butyl ether (MTBE), ethyl tert-butyl ether (ETBE), tert-amyl methyl ether (TAME), and diisopropyl ether (DIPE) were carried out in two different periods of the year (summer 2017 and winter 2018), among a large sample of healthy children (n = 736; 5–11 years old) living in rural and urban areas in central Italy. The quantification of u-MTBE, u-ETBE, u-TAME, and u-DIPE was performed by HS-SPME-GC/MS technique and information on participants was collected by a questionnaire. u-DIPE concentrations resulted always under the LOQ. u-TAME mean levels were similar in both seasons (18.7 ng L−1 in summer vs. 18.9 ng L−1 in winter), while u-MTBE and u-ETBE levels were, respectively, 69.9 and 423.5 ng L−1 (summer) and 53.3 and 66.2 ng L−1 (winter). Main predictors of urinary excretion resulted the time spent in motor vehicles, being male and younger.