The effects of meditation on arterial and tissue oxygenation are unknown and difficult to assess because respiration is often altered, directly or indirectly, during meditation practice. Thus, changes in respiration may affect cardiovascular responses independently from meditation. In this study, we aim to isolate the specific effect of meditation on arterial and tissue oxygenation and other cardiorespiratory indexes while systematically controlling for the role of respiration. Furthermore, we aim to clarify to what extent prior expertise in meditation practice is needed to observe reliable changes. Eighty participants, half with and half without prior meditation experience, were tested while pacing breathing at predetermined rates, in the presence or absence of mantra meditation instructions, and in a body scan meditation that did not involve controlled breathing. Continuous recordings were acquired for arterial and brain oxygenation, respiratory excursion, electrocardiogram, skin vasomotion, and blood pressure. In both groups, meditation acutely decreased arterial and cerebral oxygen saturation, reduced chemoreflex sensitivity, and prolonged the RR interval, independently of respiration. Conversely, slow breathing improved heart rate variability, independently of concurrent meditation. In addition to the immediate effects of meditation, the individuals with long‐term practice of meditation had overall higher arterial and cerebral oxygen saturation, overall lower blood pressure, and slower baseline respiration. Meditation acutely lowers arterial and tissue oxygenation. A repeated exposure to this condition may lead to long‐term adaptation and, through increased ventilatory efficiency and improved gas exchanges, to an increase in baseline oxygenation. Meditation induces favorable changes in cardiovascular and respiratory end points of clinical interest.