The persistent sodium current (I_NaP) plays a major role in neural pacemakers within the brainstem respiratory network. Similarities between rhythmic activities vital for embryogenesis and respiratory motor output, suggests the I_NaP may play a key role in development of the respiratory network in utero (Champagnat et al. 1997). These findings taken in conjunction with evidence for its paramount role in the ‘switching concept’, and initiation of autoresuscitative gasping behaviour post-natally (Paton et al. 2006), might suggest that a failure in mechanisms utilizing I_NaP could contribute to the pathophysiology of respiratory network disorders, such as sudden infant death syndrome (SIDS). Here, we hypothesise that the inhibition of I_NaP utero will give rise to post-natal (P) respiratory abnormalities. To test this hythesis, we administered daily riluzole (a I_NaP blocker; 10 mg/ml s.c.) to pregnant dams (Wistar rats, 302±18 g, n=2) from embryological day 10. Saline was injected as control (n=2). At birth, treatment ceased and plethsmography recordings commenced (Mortola, 1984) at days P0, P1, P2 and P7. We recorded 10 mins of rest, and 2 min of hypercapnia exposure (5%CO₂, 20%O₂, balance N₂). Values are mean±SEM and were compared with t test. Mortality, weight at birth and weight gain did not differ (P>0.05) in treated (n=20) and control rats (n=15). During quiet breathing, the riluzole treated neonatal rats (n=7) displayed a reduced tidal volume relative to control (n=7) at P7 (0.135±0.004 vs. 0.184±0.013 mL, P<0.001), and reduced respiratory frequency at P1 (125±7 vs. 146±8 breaths/min, P<0.05) and P2 (153±5 vs. 193±8 breaths/min, P<0.001). The latter was a result of both inspiratory and expiratory times being prolonged relative to the control. Moreover, riluzole treated neonates presented reduced minute ventilation at P1 (10±1 vs. 13±1 mL/min, P<0.01), P2 (14±1 vs. 19±1 mL/min, P<0.001) and P7 (24±1 vs. 36±2 mL/min, P<0.001) compared to control group. Responses to hypercapnia did not differ (P>0.05). We conclude that blockade of I_NaP during embryological development of the brainstem respiratory network affects inspiration and expiration causing a reduction of resting minute ventilation in early post-natal life. Despite previous evidence indicating a role for I_NaP in inspiratory activity only, our data also support an effect on the embryological development of expiratory activity.