Adverse exposures that influence growth in prenatal and early postnatal periods are considered to influence vulnerability to chronic diseases via their effects on the neuroendocrine system. In humans, the assessment of the underlying mechanisms has been restricted. The present study aimed to investigate the effects of adverse early-life exposures, specifically maternal mood, on hypothlamic-pituitary-adrenal (HPA) axis, sympathetic nervous system (SNS) and parasympathetic nervous system (PNS) responses to an acute physiological stressor. In addition, we conducted a preliminary examination into whether these effects varied by time of exposure and sex. One hundred and thity-nine individuals (mean age 15.12 years) were recruited from the ALSPAC (Avon Longitudinal Study of Parents and Children) birth cohort. Participants underwent the CO2 stress test and indices of the PNS, SNS and HPA axis were measured. Pre-existing data on demographic and psychosocial factors of the mothers during pregnancy (18 and 32 weeks) and postnatally (8 weeks and 8 months) were extracted, as were participants’ clinical and demographic data at birth. Increases in both pre- and postnatal anxiety and depression were associated with greater SNS reactivity to the stressor and slower recovery, as well as blunted HPA axis responses. Programming effects on the SNS appeared to be restricted to male offspring only. No consistent relationships were evident for any of the measures of pre-stress function. We have found preliminary evidence that both pre- and postnatal maternal anxiety and depression have sustained programming effects on the SNS and HPA axis. Effects on the SNS were restricted to male offspring.