Cardiovascular (CV) response to mental stress, a predictor of CV disease risk, may be determined already in utero. However, the underlying mechanisms remain unclear, and previous studies have used adult subjects and neglected CV recovery. We investigated 147 girls and 136 boys aged 8 years who underwent the Trier Social Stress Test for children to determine whether body size at birth is associated with CV activity. Blood pressure (BP), electrocardiogram and impedance-derived indices were recorded and analyzed from continuous measurements using Vasotrac APM205A and Biopac MP150 systems. Among girls, lower birth weight was associated with lower baseline systolic BP (SBP) and diastolic BP (DBP) values (1.9 mm Hg and 1.5 mm Hg per 1 s.d. birth weight for gestational age, respectively), higher SBP and DBP response to mental stress (1.6 mm Hg and 1.1 mm Hg per 1 s.d. birth weight for gestational age, respectively), slower BP recovery and overall higher cardiac sympathetic activity. In contrast, among boys lower birth weight was associated with higher baseline levels of SBP (2.1 mm Hg per 1 s.d. birth weight for gestational age) and total peripheral resistance (TPR), overall lower cardiac sympathetic activity, lower TPR response to mental stress and a more rapid BP and cardiac sympathetic recovery. In boys, the associations with baseline levels and cardiac sympathetic activity became significant only after adjusting for current body size. These sex-specific results suggest that individual differences in childhood CV response to and recovery from mental stress may have prenatal origins. This phenomenon may be important in linking smaller body size at birth to adult CV disease.