Background: Difference in pulse pressure (dPP) confirms adequate intravascular filling as a prerequisite for tissue perfusion. We hypothesized that both oxygen and dobutamine increase liver tissue oxygen tension (ptO2). Methods: Eight anesthetized pigs received dPP-guided fluid management. Hepatic pO2 was measured with Clark-type electrodes placed subcapsularly, and on the liver surface. Pigs received: (1) supplemental oxygen (FiO2 1.0); (2) dobutamine 2.5 μg/kg/min, and (3) dobutamine 5 μg/kg/min. Data were analyzed using repeated-measures ANOVA followed by a Tukey post-test for multiple comparisons. ptO2 measured subcapsularly and at the liver surface were compared using the Bland-Altman plot. Results: Variation in FiO2 changed local hepatic tissue ptO2 [subcapsular measurement: 39 ± 12 (FiO2 0.3), 89 ± 35 mm Hg (FiO2 1.0, p = 0.01 vs. FiO2 0.3), 44 ± 10 mm Hg (FiO2 0.3, p = 0.05 vs. FiO2 1.0); surface measurement: 52 ± 35 (FiO2 0.3), 112 ± 24 mm Hg (FiO2 1.0, p = 0.001 vs. FiO2 0.3), 54 ± 24 mm Hg (FiO2 0.3, p = 0.001 vs. FiO2 1.0)]. Surface measurements were widely scattered compared to subcapsular measurements (bias: –15 mm Hg, precision: 76.3 mm Hg). Dobutamine did not affect hepatic oxygenation. Conclusion: Supplemental oxygen increased hepatic tissue pO2 while dobutamine did not. Although less invasive, the use of surface measurements is discouraged.