Exposure to maternal prenatal stress that leads to elevated glucocorticoid levels has been shown to have adverse long-term effects on the offspring. This exposure results in markedly increased incidences of neurobehavioural disorders with the greatest impact on males. The links between stress exposure and behavioural disorders remain unclear but may involve glucocorticoid-induced persisting changes in inhibitory pathways. Neurosteroids are elevated during fetal life as the synthesis of these steroids in the brain is supplemented with production by the placenta. Fetal neurosteroids have major roles in neurodevelopment, particularly in promoting normal development of myelination. The placenta has a key role in protecting against the effects of prenatal stress, with placental expression of 5α-reductase type 2 (SRD5A2) leading to increased concentrations of the key neurosteroid, allopregnanolone in the fetus. Placental expression of 11β-hydroxysteroid dehydrogenase 2 (HSD11B2) that converts cortisol to less active cortisone also protects the fetus from rises in maternal cortisol. We have examined the effect of moderate psychosocial stress achieved by strobe light exposure for 2 h/day in pregnant guinea pig dams every 5 days at between gestational age 35-60 (term 70 days) on placental protective responses and long-term outcomes. Both male and females displayed an increase in placental allopregnanolone production and circulating concentrations in mid and late-gestation following repeated stress events. The female placenta displayed a greater protective response to the stress with markedly increased expression of SRD5A2 and HSD11B2, which was not seen in the male placenta. The female fetuses also displayed evidence of brain sparing at term, with normal brain weights and an increase in the brain to liver ratio. Females offspring from prenatally stressed pregnancies displayed markedly less adverse patterns of hyperactive behaviour compared to males. The greater placental responses and neurosteroid changes seen in females may explain these sex differences in long-term behavioural outcomes.