LAUSR

(1) Background: Trans-3′-hydroxy cotinine (3HC) and cotinine (COT) are tobacco smoke exposure (TSE) biomarkers and the 3HC/COT ratio is a marker of CYP2A6 activity, an enzyme which metabolizes nicotine. The primary objective was to assess the associations of these TSE biomarkers with sociodemographics and TSE patterns in children who lived with ≥1 smoker. (2) Methods: A convenience sample of 288 children (mean age (SD) = 6.42 (4.8) years) was recruited. Multiple linear regression models were built to assess associations of sociodemographics and TSE patterns with urinary biomarker response variables: (1) 3HC, (2) COT, (3) 3HC+COT sum, and (4) 3HC/COT ratio. (3) Results: All children had detectable 3HC (Geometric Mean [GeoM] = 32.03 ng/mL, 95%CI = 26.97, 38.04) and COT (GeoM = 10.24 ng/mL, 95%CI = 8.82, 11.89). Children with higher cumulative TSE had higher 3HC and COT (β^ = 0.03, 95%CI = 0.01, 0.06, p = 0.015 and β^ = 0.03, 95%CI = 0.01, 0.05, p = 0.013, respectively). Highest 3HC+COT sum levels were in children who were Black (β^ = 0.60, 95%CI = 0.04, 1.17, p = 0.039) and who had higher cumulative TSE (β^ = 0.03, 95%CI = 0.01, 0.06, p = 0.015). Lowest 3HC/COT ratios were in children who were Black (β^ = −0.42, 95%CI = −0.78, −0.07, p = 0.021) and female (β^ = −0.32, 95%CI = −0.62, −0.01, p = 0.044). (4) Conclusion: Results indicate that there are racial and age-related differences in TSE, most likely due to slower nicotine metabolism in non-Hispanic Black children and in younger children.