BACKGROUND: In preterm neonates, the cardiovascular and cerebral vascular control is immature, making the brain vulnerable to an increased incidence of hypoxic and hyperoxic episodes. AIM: The aim of the study was to apply the recently developed multiple Einstein's cross wavelet analysis (MECWA) to quantify the coupling of fluctuations of peripherally measured arterial oxygen saturation (SpO2), cerebral tissue oxygen saturation (StO2) and heart rate (HR). METHODS: Two long-term measurements on preterm neonates with a gestational age at birth of 26.4 and 26.8 weeks and a postnatal age of 2.1 and 3.9 weeks were analyzed. MECWA was applied to SpO2, StO2 and HR. RESULTS: MECWA showed that the fluctuations of SpO2, StO2 and HR were synchronized in the low-frequency range with periods of ~1 h and ~0.5 h. The amplitudes of the synchronization frequencies were dependent on the individual neonate. DISCUSSION: MECWA is a useful novel tool to assess the coupling of physiological signals. The parameters determined by MECWA seem to be related to the chronobiological processes, as well as constant regulations of the cardiovascular and cerebral perfusion state. CONCLUSION: MECWA was able to identify long-term synchronization of the cardiovascular and cerebral perfusion state in preterm neonates with periods of ~1 h and ~0.5 h.