This prospective longitudinal study evaluated multiple maternal biomarkers from the preconception and prenatal periods as time-sensitive predictors of child executive functioning (EF) in 100 mother-child dyads. Maternal glycated hemoglobin (HbA1C ), C-reactive protein (CRP), and blood pressure (BP) were assayed before pregnancy and during the second and third trimesters. Subsequently, children were followed from birth and assessed for EF (i.e. cognitive flexibility, response inhibition) at ages 4-6 years. Perinatal data were also extracted from neonatal records. Higher maternal CRP, but not maternal HbA1C or BP, uniquely predicted poorer child cognitive flexibility, even with control of maternal HbA1C and BP, relevant demographic factors, and multiple prenatal/perinatal covariates (i.e. preconception maternal body mass index, maternal depression, maternal age at birth, child birth weight, child birth order, child gestational age, and child birth/neonatal complications). Predictions from maternal CRP were specific to the third trimester, and third trimester maternal CRP robustly predicted child cognitive flexibility independently of preconception and second trimester CRP. Child response inhibition was unrelated to maternal biomarkers from all time points. These findings provide novel, prospective evidence that maternal inflammation uniquely predicts child cognitive flexibility deficits, and that these associations depend on the timing of exposure before or during pregnancy.