Background: Prenatal and early-life periods may be critical windows for harmful effects of air pollution on infant health.Objectives: We studied the association of air pollution exposure during pregnancy and the first year of life with respiratory illnesses, ear infections, and eczema during the first 12–18 months of age in a Spanish birth cohort of 2,199 infants.Methods: We obtained parentally reported information on doctor-diagnosed lower respiratory tract infections (LRTI) and parental reports of wheezing, eczema, and ear infections. We estimated individual exposures to nitrogen dioxide (NO2) and benzene with temporally adjusted land use regression models. We used log-binomial regression models and a combined random-effects meta-analysis to estimate the effects of air pollution exposure on health outcomes across the four study locations.Results: A 10-µg/m3 increase in average NO2 during pregnancy was associated with LRTI [relative risk (RR) = 1.05; 95% CI: 0.98, 1.12] and ear infections (RR = 1.18; 95% CI: 0.98, 1.41). The RRs for an interquartile range (IQR) increase in NO2 were 1.08 (95% CI: 0.97, 1.21) for LRTI and 1.31 (95% CI: 0.97, 1.76) for ear infections. Compared with NO2, the association for an IQR increase in average benzene exposure was similar for LRTI (RR = 1.06; 95% CI: 0.94, 1.19) and slightly lower for ear infections (RR = 1.17; 95% CI: 0.93, 1.46). Associations were slightly stronger among infants whose mothers spent more time at home during pregnancy. Air pollution exposure during the first year was highly correlated with prenatal exposure, so we were unable to discern the relative importance of each exposure period.Conclusions: Our findings support the hypothesis that early-life exposure to ambient air pollution may increase the risk of upper and lower respiratory tract infections in infants.