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Background Pulmonary dead space (VD) is an index of ventilation inhomogeneity and one of the determinants of the magnitude of tidal volume to maintain optimal blood gases. Aims To identify the determinants of VD in ventilated newborns and to investigate differences in VD between prematurely born and term infants and those prematurely born infants who did or did not develop bronchopulmonary dysplasia (BPD). Methods Sixty-one mechanically ventilated infants (15 term, 46 preterm) were studied at a median age of 8 (IQR 2–31) days; 32 of the preterm infants developed BPD. VD was determined from the difference between arterial and end tidal carbon dioxide (CO2) using a low dead space CO2 detector using the Bohr/Enghoff equation and was related to body weight (VD/kg) at the time of study. The time to peak tidal expiratory flow/expiratory time (TPTEF/TE) was measured during spontaneous breathing using a fixed orifice pneumotachograph. Results VD/kg was related to gestational age (r = − 0.285, p = 0.001), birth weight (r = − 0.356, p < 0.001), weight (r = − 0.316, p < 0.001) and postmenstrual age (r = − 0.205, p = 0.020) at measurement, days of ventilation (r = 0.322, p < 0.001) and TPTEF/TE (r = − 0.397, p = 0.003). The median VD/kg was higher in prematurely born infants [2.3 (IQR: 1.7–3.0) ml/kg] compared to term infants [1.5 (1.3–2.1) ml/kg, (p = 0.003)] and in premature infants that developed BPD [2.6 (IQR 1.8–3.4) ml/kg] compared to those who did not [1.7 (IQR 1.1–1.9) ml/kg], (p < 0.001). Conclusions Numerous factors influence pulmonary dead space and thus an optimum tidal volume will differ according to the underlying demographics and respiratory status.