In Wild Type (WT) and serotonin transporter (5HTT) null mice, we studied oxygen consumption, ventilation and heart rate in air and 5% CO2 at postnatal (P) days P5, P15, and P25 using either a head-out (younger mice) or whole body plethysmograph (older mice). Body weight and temperature did not differ between the groups. Oxygen consumption differed significantly only in females at P15 when it was reduced in 5HTT nulls (P < 0.01). Heart rate similarly differed only in female 5HTT nulls at P15 being decreased in both air and CO2 (P < 0.01). Ventilation in air and 5% CO2 was significant reduced via an effect on tidal volume at P15 (P < 0.02) and P25 (P < 0.05) but only in males. Ventilation in air and 5% CO2 was greater in 5HTT null females at P25. We conclude that the gender specific effect (male predominant) on the CO2 response reported in 5HTT null adult mice (Li and Nattie, 2008, J. Physiol. 586.9, 2321–2329, 2008) appears to have origins in early postnatal life (P15) when ventilation in both air and 5% CO2 is reduced.