Background and objective: Clonidine, which is used for induction of sympatholysis and prevention or treatment of alcohol withdrawal in anaesthesia and intensive care medicine, may have deleterious effects on intestinal mucosal perfusion. This study was designed to investigate the effects of clonidine on intestinal perfusion and oxygenation. Methods: Following ethical approval 17 anaesthetized, and acutely instrumented pigs were randomly assigned to two groups: eight animals received intravenous clonidine (2 μg kg−1 bolus and 2 μg kg−1 h−1), nine animals served as a control group. Measurement points for systemic and regional haemodynamic and oxygenation parameters were 135 and 315 min after starting the clonidine application. Results: Clonidine elicited systemic haemodynamic changes (median [25–75th interquartile range]): heart rate (106 [91, 126] to 84 [71, 90] beats min−1) cardiac output (147 [123, 193] to 90 [87, 107] mL min−1 kg−1) and mean arterial pressure (77 [72, 93] to 69 [61, 78] mmHg) decreased. Despite systemic haemodynamic changes, the superior mesenteric artery blood flow did not change in the clonidine group. The vascular resistance of the superior mesenteric artery decreased. The small intestinal oxygen supply, the mucosal and the serosal tissue oxygen partial pressure did not change. Conclusions: Systemic sympatholysis induced by intravenously applied clonidine in addition to basic intravenous anaesthesia elicited a decrease in cardiac output and mean arterial pressure. However, regional macrohaemodynamic perfusion was maintained and intestinal oxygenation did not change. Clonidine does not impair intestinal mucosal and serosal oxygenation under physiological conditions.