Background: The rostral ventrolateral medulla (RVLM) maintains sympathetic nerve activity (SNA), and integrates adaptive reflexes. Orexin A (OX-A)-immunoreactive (-ir) neurones in the lateral hypothalamus project to the RVLM. Microinjection of OX-A into RVLM increases blood pressure and heart rate (HR). The expression of orexin receptors, and effect of OX-A in the RVLM on splanchnic SNA (sSNA), respiration and adaptive reflexes is unknown. Experimental approach: The effect of OX-A on baseline cardiorespiratory variables as well as the somatosympathetic, baroreceptor and chemoreceptor reflexes in RVLM were investigated in urethane-anaesthetized, vagotomized and artificially ventilated male Sprague-Dawley rats (n = 49). OX-A and its receptors were detected with fluorescence immunohistochemistry. Key results: RVLM tyrosine hydroxylase-ir (TH-ir) neurones were frequently colocalised with orexin receptor 1 (OX₁) and orexin receptor 2 (OX₂), and closely apposed by OX-A-ir terminals. RVLM injection of OX-A is pressor and sympathoexcitatory. The peak effect was observed at 50 pmol with increase in mean arterial pressure (MAP) and SNA of 42 mmHg and 45 % from baseline, respectively. The responses to OX-A (50 pmol) were attenuated by the OX₁ antagonist, SB334867, and reproduced by the OX₂ agonist, [Ala₁₁, D-Leu₁₅]orexin B. OX-A attenuated the somatosympathetic reflex but increased baroreflex sensitivity. OX-A increased or reduced the sympathoexcitation following hypoxia or hypercapnia respectively. Conclusions: The results demonstrate that while the central cardiorespiratory control mechanisms at rest do not rely on orexin, responses to adaptive stimuli are dramatically affected by the functional state of orexin receptors.