β-Blockers are used in pregnancy-associated hypertension and in postnatal cardiac arrhythmias, and the neonate may get them in breast milk. We therefore studied the effects of β-adrenergic medication on interrelations between heart rate (HR), respiration, and arterial blood pressure (aBP) in newborn lambs. The influence of sleep state on these cardiorespiratory interrelations was also examined. HR, aBP, and respiration (based on transthorack electrical impedance) were recorded and the sleep state was visually documented in five healthy chronically instrumented newborn lambs before the age of 30 d. Propranolol was given (1 mg/kg). Two-min stationary segments of the three signals were analyzed using a multivariate autoregressive model, which yields oscillations of the signals and intersignal relationships as source contributions. The variabilities of aBP and HR were greatest at the low frequencies (<0.25 Hz) and so were their intersignal relationships (including baroreflex). The respiratory variability was greatest at the frequencies corresponding to the respiratory rate. Daring quiet sleep, the variabilities in HR, aBP, and respiration were lowest. The impact of respiratory oscillations on other signals increased but the impact of aBP variability decreased during quiet sleep. β-Blockade and sleep state affected separately the cardiovascular and respiratory variables and their interrelations. β-Blockade reduced HR and increased pulse pressure. The overall heart rate variability and the respiratory low-frequency contribution to heart rate variability decreased due to the β-blockade. We postulate that the β-adrenergic system is an important regulator of HR and HR variability IB neonatal lambs and also of the low-frequency components of the respiratory sinus arrhythmia. However, inasmuch as the interrelations between HR and aBP were not altered by the β-blockade, even high doses of propranolol do not seem hazardous for the cardiovascular system in neonatal lambs.