Background: Non-invasive monitoring of cerebral tissue oxygen saturation (rcSO 2) during transition is of growing interest. Different near-infrared spectroscopy (NIRS) techniques have been developed to measure rcSO 2. We compared rcSO 2 values during the immediate transition in preterm neonates measured with frequency-domain NIRS (FD-NIRS) with those measured with continuous-wave NIRS (CW-NIRS) devices in prospective observational studies. Methods: We compared rcSO 2 values measured with an FD-NIRS device during the first 15 min after birth in neonates with a gestational age ≥ 30 weeks but < 37 weeks born at the Erasmus MC-Sophia Children's Hospital, Rotterdam, the Netherlands, with similar values measured with a CW-NIRS device in neonates born at the Medical University of Graz, Austria. Mixed models were used to adjust for repeated rcSO 2 measurements, with fixed effects for time (non-linear), device, respiratory support and the interaction of device and respiratory support with time. Additionally, parameters such as total haemoglobin concentration and oxygenated and deoxygenated haemoglobin concentrations measured by FD-NIRS were analysed. Results: Thirty-eight FD-NIRS measurements were compared with 58 CW-NIRS measurements. The FD-NIRS rcSO 2 values were consistently higher than the CW-NIRS rcSO 2 values in the first 12 min, irrespective of respiratory support. After adjustment for respiratory support, the time-dependent trend in rcSO 2 differed significantly between techniques (p < 0.01). Conclusion: As cerebral saturation measured with the FD-NIRS device differed significantly from that measured with the CW-NIRS device, differences in absolute values need to be interpreted with care. Although FD-NIRS devices have technical advantages over CW-NIRS devices, FD-NIRS devices may overestimate true cerebral oxygenation and their benefits might not outweigh the usability of the more clinically viable CW-NIRS devices.